Publications that have used Kaha Sciences telemetry systems (including previous company names Millar and Telemetry Research):
2017 |
|
Squair, J W; West, C R; Popok, D; Assinck, P; Liu, J; Tetzlaff, W; Krassioukov, A V High Thoracic Contusion Model for the Investigation of Cardiovascular Function after Spinal Cord Injury Journal Article Journal of neurotrauma, 34 (3), pp. 671-684, 2017, ISBN: 1557-9042. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TRM56SP @article{RefWorks:doc:5c74bf9fe4b00e57e1f36625,
title = {High Thoracic Contusion Model for the Investigation of Cardiovascular Function after Spinal Cord Injury}, author = {J W Squair and C R West and D Popok and P Assinck and J Liu and W Tetzlaff and A V Krassioukov}, doi = {10.1089/neu.2016.4518}, isbn = {1557-9042}, year = {2017}, date = {2017-02-01}, journal = {Journal of neurotrauma}, volume = {34}, number = {3}, pages = {671-684}, abstract = {Cardiovascular disease is the leading cause of death for individuals with spinal cord injury (SCI). Because of a lack of a standardized and accessible animal model for cardiovascular disease after SCI, few laboratories have conducted pre-clinical trials aimed at reinstating descending cardiovascular control. Here, we utilized common contusion methodology applied to the midline of the upper-thoracic cord of adult Wistar rats accompanied with telemetric blood pressure monitoring and FluoroGold retrograde neuronal tracing, as well as lesion site and lumbrosacral afferent immunohistochemistry. We demonstrate widespread cardiovascular (i.e., impaired resting hemodynamics, autonomic dysreflexia) and hindlimb dysfunction at 1 month post-injury. Further, we provide a description of the neuroanatomical changes that accompany cardiovascular abnormalities. Specifically, we describe 1) the injury site including white matter sparing as well as lesion volume, and their correlations to cardiovascular as well as motor outcomes; 2) the severity of injury-dependent changes in sympathoexcitatory medullary neuron spinal connectivity, as measured using FluoroGold tracing; and 3) the extent of aberrant afferent plasticity within the lumbosacral region of the spinal cord, which has been linked to the development of autonomic dysreflexia. We believe that this model, which utilizes equipment common to numerous SCI laboratories, can serve as a research standard for studies specifically aimed at investigating autonomic neuroprotective and regenerative strategies following SCI.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TRM56SP}, pubstate = {published}, tppubtype = {article} } Cardiovascular disease is the leading cause of death for individuals with spinal cord injury (SCI). Because of a lack of a standardized and accessible animal model for cardiovascular disease after SCI, few laboratories have conducted pre-clinical trials aimed at reinstating descending cardiovascular control. Here, we utilized common contusion methodology applied to the midline of the upper-thoracic cord of adult Wistar rats accompanied with telemetric blood pressure monitoring and FluoroGold retrograde neuronal tracing, as well as lesion site and lumbrosacral afferent immunohistochemistry. We demonstrate widespread cardiovascular (i.e., impaired resting hemodynamics, autonomic dysreflexia) and hindlimb dysfunction at 1 month post-injury. Further, we provide a description of the neuroanatomical changes that accompany cardiovascular abnormalities. Specifically, we describe 1) the injury site including white matter sparing as well as lesion volume, and their correlations to cardiovascular as well as motor outcomes; 2) the severity of injury-dependent changes in sympathoexcitatory medullary neuron spinal connectivity, as measured using FluoroGold tracing; and 3) the extent of aberrant afferent plasticity within the lumbosacral region of the spinal cord, which has been linked to the development of autonomic dysreflexia. We believe that this model, which utilizes equipment common to numerous SCI laboratories, can serve as a research standard for studies specifically aimed at investigating autonomic neuroprotective and regenerative strategies following SCI.
|
|
Qiao, X; Zhou, J J; Li, D P; Pan, H L Src Kinases Regulate Glutamatergic Input to Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension Journal Article Hypertension (Dallas, Tex.: 1979), 69 (1), pp. 154-162, 2017, ISBN: 1524-4563. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM54P @article{RefWorks:doc:5c74bf8be4b01022d49dea4b,
title = {Src Kinases Regulate Glutamatergic Input to Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension}, author = {X Qiao and J J Zhou and D P Li and H L Pan}, url = {https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.116.07947}, isbn = {1524-4563}, year = {2017}, date = {2017-01-01}, journal = {Hypertension (Dallas, Tex.: 1979)}, volume = {69}, number = {1}, pages = {154-162}, abstract = {The elevated sympathetic outflow associated with hypertension is maintained by increased N-methyl-d-aspartate receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus. Synaptic NMDAR activity is tightly regulated by protein kinases, including the Src family of tyrosine kinases. We determined whether Src kinases play a role in increased NMDAR activity of PVN neurons projecting to the rostral ventrolateral medulla and in elevated sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs). The Src protein level in the PVN was significantly greater in SHRs than in normotensive Wistar-Kyoto (WKY) rats and was not significantly altered by lowering blood pressure with celiac ganglionectomy in SHRs. Inhibition of Src kinase activity with 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) completely normalized the higher amplitudes of evoked NMDAR-mediated excitatory postsynaptic currents and puff NMDA-elicited currents of rostral ventrolateral medulla-projecting PVN neurons in SHRs. PP2 treatment also attenuated the higher frequency of NMDAR-mediated miniature excitatory postsynaptic currents of these neurons in SHRs. However, PP2 had no effect on NMDAR-excitatory postsynaptic currents or miniature excitatory postsynaptic currents of rostral ventrolateral medulla-projecting PVN neurons in WKY rats. NMDAR activity increased by an Src-activating peptide was blocked by PP2 but not by inhibition of casein kinase 2. In addition, microinjection of PP2 into the PVN not only decreased lumbar sympathetic nerve discharges and blood pressure but also eliminated the inhibitory effect of the NMDAR antagonist on sympathetic nerve activity and blood pressure in SHRs. Collectively, our findings suggest that increased Src kinase activity potentiates presynaptic and postsynaptic NMDAR activity in the PVN and sympathetic vasomotor tone in hypertension.}, keywords = {Blood Pressure, Rat, TRM54P}, pubstate = {published}, tppubtype = {article} } The elevated sympathetic outflow associated with hypertension is maintained by increased N-methyl-d-aspartate receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus. Synaptic NMDAR activity is tightly regulated by protein kinases, including the Src family of tyrosine kinases. We determined whether Src kinases play a role in increased NMDAR activity of PVN neurons projecting to the rostral ventrolateral medulla and in elevated sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs). The Src protein level in the PVN was significantly greater in SHRs than in normotensive Wistar-Kyoto (WKY) rats and was not significantly altered by lowering blood pressure with celiac ganglionectomy in SHRs. Inhibition of Src kinase activity with 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) completely normalized the higher amplitudes of evoked NMDAR-mediated excitatory postsynaptic currents and puff NMDA-elicited currents of rostral ventrolateral medulla-projecting PVN neurons in SHRs. PP2 treatment also attenuated the higher frequency of NMDAR-mediated miniature excitatory postsynaptic currents of these neurons in SHRs. However, PP2 had no effect on NMDAR-excitatory postsynaptic currents or miniature excitatory postsynaptic currents of rostral ventrolateral medulla-projecting PVN neurons in WKY rats. NMDAR activity increased by an Src-activating peptide was blocked by PP2 but not by inhibition of casein kinase 2. In addition, microinjection of PP2 into the PVN not only decreased lumbar sympathetic nerve discharges and blood pressure but also eliminated the inhibitory effect of the NMDAR antagonist on sympathetic nerve activity and blood pressure in SHRs. Collectively, our findings suggest that increased Src kinase activity potentiates presynaptic and postsynaptic NMDAR activity in the PVN and sympathetic vasomotor tone in hypertension.
|
2016 |
|
Kawoos, U; Gu, M; Lankasky, J; McCarron, R M; Chavko, M Effects of Exposure to Blast Overpressure on Intracranial Pressure and Blood-Brain Barrier Permeability in a Rat Model Journal Article PloS one, 11 (12), pp. e0167510, 2016, ISBN: 1932-6203. Abstract | Links | BibTeX | Tags: Intracranial Pressure, Rat, TRM54P25 @article{RefWorks:doc:5c74be44e4b01022d49dea35,
title = {Effects of Exposure to Blast Overpressure on Intracranial Pressure and Blood-Brain Barrier Permeability in a Rat Model}, author = {U Kawoos and M Gu and J Lankasky and R M McCarron and M Chavko}, doi = {10.1371/journal.pone.0167510}, isbn = {1932-6203}, year = {2016}, date = {2016-12-01}, journal = {PloS one}, volume = {11}, number = {12}, pages = {e0167510}, abstract = {Exposure to blast overpressure (BOP) activates a cascade of pathological processes including changes in intracranial pressure (ICP) and blood-brain barrier (BBB) permeability resulting in traumatic brain injury (TBI). In this study the effect of single and multiple exposures at two intensities of BOP on changes in ICP and BBB permeability in Sprague-Dawley rats was evaluated. Animals were exposed to a single or three repetitive (separated by 0.5 h) BOPs at 72 kPa or 110 kPa. ICP was monitored continuously via telemetry for 6 days after exposure to BOP. The alteration in the permeability of BBB was determined by extravasation of Evans Blue (EB) into brain parenchyma. A significant increase in ICP was observed in all groups except the single 72 kPa BOP group. At the same time a marked increase in BBB permeability was also seen in various parts of the brain. The extent of ICP increase as well as BBB permeability change was dependent on intensity and frequency of blast.}, keywords = {Intracranial Pressure, Rat, TRM54P25}, pubstate = {published}, tppubtype = {article} } Exposure to blast overpressure (BOP) activates a cascade of pathological processes including changes in intracranial pressure (ICP) and blood-brain barrier (BBB) permeability resulting in traumatic brain injury (TBI). In this study the effect of single and multiple exposures at two intensities of BOP on changes in ICP and BBB permeability in Sprague-Dawley rats was evaluated. Animals were exposed to a single or three repetitive (separated by 0.5 h) BOPs at 72 kPa or 110 kPa. ICP was monitored continuously via telemetry for 6 days after exposure to BOP. The alteration in the permeability of BBB was determined by extravasation of Evans Blue (EB) into brain parenchyma. A significant increase in ICP was observed in all groups except the single 72 kPa BOP group. At the same time a marked increase in BBB permeability was also seen in various parts of the brain. The extent of ICP increase as well as BBB permeability change was dependent on intensity and frequency of blast.
|
|
Pena, Dela I J I; Kim, H J; de la Pena, J B; Kim, M; Botanas, C J; You, K Y; Woo, T; Lee, Y S; Jung, J C; Kim, K M; Cheong, J H A tryptic hydrolysate from bovine milk alphas1-casein enhances pentobarbital-induced sleep in mice via the GABAA receptor Journal Article Behavioural brain research, 313 , pp. 184-190, 2016, ISBN: 1872-7549. Abstract | Links | BibTeX | Tags: EEG, Rat, TR50B @article{RefWorks:doc:5c74be2ae4b073ca706afd0a,
title = {A tryptic hydrolysate from bovine milk alphas1-casein enhances pentobarbital-induced sleep in mice via the GABAA receptor}, author = {I J I Dela Pena and H J Kim and J B de la Pena and M Kim and C J Botanas and K Y You and T Woo and Y S Lee and J C Jung and K M Kim and J H Cheong}, doi = {10.1016/j.bbr.2016.07.013}, isbn = {1872-7549}, year = {2016}, date = {2016-10-01}, journal = {Behavioural brain research}, volume = {313}, pages = {184-190}, abstract = {Studies have shown that enzymatic hydrolysis of casein, the primary protein component of cow's milk, produces peptides with various biological activities, and some of these peptides may have sleep-promoting effects. In the present study, we evaluated the sedative and sleep-promoting effects of bovine alphaS1-casein tryptic hydrolysate (CH), containing a decapeptide alphaS1-casein known as alpha-casozepine. CH was orally administered to ICR mice at various concentrations (75, 150, 300, or 500mg/kg). An hour after administration, assessment of its sedative (open-field and rota-rod tests) and sleep-potentiating effects (pentobarbital-induced sleeping test and EEG monitoring) were conducted. Although a trend can be observed, CH treatment did not significantly alter the spontaneous locomotor activity and motor function of mice in the open-field and rota-rod tests. On the other hand, CH (150mg/kg, respectively) enhanced the sleep induced by pentobarbital sodium in mice. It also promoted slow-wave (delta) EEG activity in rats; a pattern indicative of sleep or relaxation. These behavioral results indicate that CH has sleep-promoting effects, but no or has minimal sedative effects. To elucidate the probable mechanism behind the effects of CH, we examined its action on intracellular chloride ion influx in cultured human neuroblastoma cells. CH dose-dependently increased chloride ion influx, which was blocked by co-administration of bicuculline, a competitive GABAA receptor antagonist. Taken together, the results of the present study suggest that CH has sleep-promoting properties which are probably mediated through the GABAA receptor-chloride ion channel complex.}, keywords = {EEG, Rat, TR50B}, pubstate = {published}, tppubtype = {article} } Studies have shown that enzymatic hydrolysis of casein, the primary protein component of cow's milk, produces peptides with various biological activities, and some of these peptides may have sleep-promoting effects. In the present study, we evaluated the sedative and sleep-promoting effects of bovine alphaS1-casein tryptic hydrolysate (CH), containing a decapeptide alphaS1-casein known as alpha-casozepine. CH was orally administered to ICR mice at various concentrations (75, 150, 300, or 500mg/kg). An hour after administration, assessment of its sedative (open-field and rota-rod tests) and sleep-potentiating effects (pentobarbital-induced sleeping test and EEG monitoring) were conducted. Although a trend can be observed, CH treatment did not significantly alter the spontaneous locomotor activity and motor function of mice in the open-field and rota-rod tests. On the other hand, CH (150mg/kg, respectively) enhanced the sleep induced by pentobarbital sodium in mice. It also promoted slow-wave (delta) EEG activity in rats; a pattern indicative of sleep or relaxation. These behavioral results indicate that CH has sleep-promoting effects, but no or has minimal sedative effects. To elucidate the probable mechanism behind the effects of CH, we examined its action on intracellular chloride ion influx in cultured human neuroblastoma cells. CH dose-dependently increased chloride ion influx, which was blocked by co-administration of bicuculline, a competitive GABAA receptor antagonist. Taken together, the results of the present study suggest that CH has sleep-promoting properties which are probably mediated through the GABAA receptor-chloride ion channel complex.
|
|
Silva, L E; Lataro, R M; Castania, J A; da Silva, C A; Valencia, J F; Murta, L O; Salgado, H C; Fazan, R; Porta, A American journal of physiology.Regulatory, integrative and comparative physiology, 311 (1), pp. 150, 2016, ISBN: 1522-1490. Abstract | Links | BibTeX | Tags: ECG, Rat, TR50B @article{RefWorks:doc:5c74bed7e4b063d617047e0c,
title = {Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches}, author = {L E Silva and R M Lataro and J A Castania and C A da Silva and J F Valencia and L O Murta and H C Salgado and R Fazan and A Porta}, doi = {10.1152/ajpregu.00076.2016}, isbn = {1522-1490}, year = {2016}, date = {2016-07-01}, journal = {American journal of physiology.Regulatory, integrative and comparative physiology}, volume = {311}, number = {1}, pages = {150}, abstract = {The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation.}, keywords = {ECG, Rat, TR50B}, pubstate = {published}, tppubtype = {article} } The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation.
|
|
Botanas, C J; Lee, H; de la Pena, J B; Pena, Dela I J; Woo, T; Kim, H J; Han, D H; Kim, B N; Cheong, J H Physiology & Behavior, 155 , pp. 30-37, 2016, ISBN: 1873-507X. Abstract | Links | BibTeX | Tags: EEG, Rat, TR50B @article{RefWorks:doc:5c74be10e4b08c84ab03efc7,
title = {Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder}, author = {C J Botanas and H Lee and J B de la Pena and Dela I J Pena and T Woo and H J Kim and D H Han and B N Kim and J H Cheong}, doi = {10.1016/j.physbeh.2015.11.035}, isbn = {1873-507X}, year = {2016}, date = {2016-03-01}, journal = {Physiology & Behavior}, volume = {155}, pages = {30-37}, abstract = {Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms.}, keywords = {EEG, Rat, TR50B}, pubstate = {published}, tppubtype = {article} } Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms.
|
|
Alvarez-Argote, S; Gransee, H M; Mora, J C; Stowe, J M; Jorgenson, A J; Sieck, G C; Mantilla, C B The Impact of Midcervical Contusion Injury on Diaphragm Muscle Function Journal Article Journal of neurotrauma, 33 (5), pp. 500-509, 2016, ISBN: 1557-9042. Abstract | Links | BibTeX | Tags: EMG, Rat, TR50BB @article{RefWorks:doc:5c749dade4b02df9431d7ced,
title = {The Impact of Midcervical Contusion Injury on Diaphragm Muscle Function}, author = {S Alvarez-Argote and H M Gransee and J C Mora and J M Stowe and A J Jorgenson and G C Sieck and C B Mantilla}, doi = {10.1089/neu.2015.4054}, isbn = {1557-9042}, year = {2016}, date = {2016-03-01}, journal = {Journal of neurotrauma}, volume = {33}, number = {5}, pages = {500-509}, abstract = {Midcervical contusion injuries disrupt descending ipsilateral excitatory bulbospinal projections to phrenic motoneurons, compromising ventilation. We hypothesized that a unilateral contusion injury at C3 versus C5 would differentially impact phrenic activity reflecting more prominent disruption of ipsilateral descending excitatory drive to more caudal segments of the phrenic motor pool with more cranial injuries. Phrenic motoneuron counts and evidence of diaphragm muscle denervation at individual neuromuscular junctions (NMJ) were evaluated at 14 days post-injury after unilateral contusion injury (100 kDynes). Whole body plethysmography and chronic diaphragm EMG were measured before the injury and at 3, 7, and 14 days post-injury. Contusion injuries at either level resulted in a similarly sized cavity. C3 contusion resulted in loss of 39 +/- 13% of ipsilateral phrenic motoneurons compared with 13 +/- 21% after C5 contusion (p = 0.003). Cervical contusion injuries resulted in diaphragm muscle denervation (C3 contusion: 17 +/- 4%; C5 contusion: 7 +/- 4%; p = 0.047). The pattern of denervation revealed segmental innervation of the diaphragm muscle, with greater denervation ventrally after C3 contusion and dorsally after C5 contusion. Overall, diaphragm root mean square electromyography activity did not change ipsilaterally after C3 or C5 contusion, but increased contralaterally ( approximately 11%) after C3 contusion only on the first day post-injury (p = 0.026). Similarly, there were no significant changes in breathing parameters during eupnea or exposure to hypoxia (10% O2) - hypercapnia (5% CO2) at any time post-injury. Unilateral midcervical contusions minimally impair ventilatory behaviors despite phrenic motoneuron loss and diaphragm muscle denervation.}, keywords = {EMG, Rat, TR50BB}, pubstate = {published}, tppubtype = {article} } Midcervical contusion injuries disrupt descending ipsilateral excitatory bulbospinal projections to phrenic motoneurons, compromising ventilation. We hypothesized that a unilateral contusion injury at C3 versus C5 would differentially impact phrenic activity reflecting more prominent disruption of ipsilateral descending excitatory drive to more caudal segments of the phrenic motor pool with more cranial injuries. Phrenic motoneuron counts and evidence of diaphragm muscle denervation at individual neuromuscular junctions (NMJ) were evaluated at 14 days post-injury after unilateral contusion injury (100 kDynes). Whole body plethysmography and chronic diaphragm EMG were measured before the injury and at 3, 7, and 14 days post-injury. Contusion injuries at either level resulted in a similarly sized cavity. C3 contusion resulted in loss of 39 +/- 13% of ipsilateral phrenic motoneurons compared with 13 +/- 21% after C5 contusion (p = 0.003). Cervical contusion injuries resulted in diaphragm muscle denervation (C3 contusion: 17 +/- 4%; C5 contusion: 7 +/- 4%; p = 0.047). The pattern of denervation revealed segmental innervation of the diaphragm muscle, with greater denervation ventrally after C3 contusion and dorsally after C5 contusion. Overall, diaphragm root mean square electromyography activity did not change ipsilaterally after C3 or C5 contusion, but increased contralaterally ( approximately 11%) after C3 contusion only on the first day post-injury (p = 0.026). Similarly, there were no significant changes in breathing parameters during eupnea or exposure to hypoxia (10% O2) - hypercapnia (5% CO2) at any time post-injury. Unilateral midcervical contusions minimally impair ventilatory behaviors despite phrenic motoneuron loss and diaphragm muscle denervation.
|
|
Rossi, N F; Pajewski, R; Chen, H; Littrup, P J; Maliszewska-Scislo, M American journal of physiology.Regulatory, integrative and comparative physiology, 310 (2), pp. 197, 2016, ISBN: 1522-1490. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c74be75e4b00e57e1f3660d,
title = {Hemodynamic and neural responses to renal denervation of the nerve to the clipped kidney by cryoablation in two-kidney, one-clip hypertensive rats}, author = {N F Rossi and R Pajewski and H Chen and P J Littrup and M Maliszewska-Scislo}, doi = {10.1152/ajpregu.00331.2015}, isbn = {1522-1490}, year = {2016}, date = {2016-01-01}, journal = {American journal of physiology.Regulatory, integrative and comparative physiology}, volume = {310}, number = {2}, pages = {197}, abstract = {Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was approximately 85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was approximately 85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.
|
|
Moya, E A; Arias, P; Varela, C; Oyarce, M P; Rio, Del R; Iturriaga, R Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation Journal Article Oxidative medicine and cellular longevity, 2016 , pp. 9802136, 2016, ISBN: 1942-0994. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM54P @article{RefWorks:doc:5c74be5ee4b073ca706afd22,
title = {Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation}, author = {E A Moya and P Arias and C Varela and M P Oyarce and Del R Rio and R Iturriaga}, doi = {10.1155/2016/9802136}, isbn = {1942-0994}, year = {2016}, date = {2016-01-01}, journal = {Oxidative medicine and cellular longevity}, volume = {2016}, pages = {9802136}, abstract = {Oxidative stress is involved in the development of carotid body (CB) chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO(-)), a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO(-) scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) in the CB, the CB chemosensory discharge, and arterial blood pressure (BP) in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day) for 7 days. Ebselen (10 mg/kg/day) was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 +/- 14.9 versus 22.9 +/- 4.2 a.u.), reduced CB chemosensory response to 5% O2 (266.5 +/- 13.4 versus 168.6 +/- 16.8 Hz), and decreased mean BP (116.9 +/- 13.2 versus 82.1 +/- 5.1 mmHg). Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO(-) formation.}, keywords = {Blood Pressure, Rat, TRM54P}, pubstate = {published}, tppubtype = {article} } Oxidative stress is involved in the development of carotid body (CB) chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO(-)), a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO(-) scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) in the CB, the CB chemosensory discharge, and arterial blood pressure (BP) in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day) for 7 days. Ebselen (10 mg/kg/day) was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 +/- 14.9 versus 22.9 +/- 4.2 a.u.), reduced CB chemosensory response to 5% O2 (266.5 +/- 13.4 versus 168.6 +/- 16.8 Hz), and decreased mean BP (116.9 +/- 13.2 versus 82.1 +/- 5.1 mmHg). Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO(-) formation.
|
|
Emans, Tonja W; Janssen, Ben J; Pinkham, Maximilian I; Ow, Connie P C; Evans, Roger G; Joles, Jaap A; Malpas, Simon C; Krediet, Paul C T; Koeners, Maarten P Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow Journal Article The Journal of Physiology, 594 (21), pp. 6287-6300, 2016, ISBN: 1469-7793. Abstract | Links | BibTeX | Tags: Oxygen, TR57Y @article{RefWorks:doc:5c0dbbd8e4b0788332691c5d,
title = {Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow}, author = {Tonja W Emans and Ben J Janssen and Maximilian I Pinkham and Connie P C Ow and Roger G Evans and Jaap A Joles and Simon C Malpas and Paul C T Krediet and Maarten P Koeners}, doi = {10.1113/JP270731}, isbn = {1469-7793}, year = {2016}, date = {2016-00-01}, journal = {The Journal of Physiology}, volume = {594}, number = {21}, pages = {6287-6300}, abstract = {KEY POINTS: Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. ABSTRACT: We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min-1 . Equi-pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin-angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PO2. This could be reversed within minutes by pharmacological angiotensin-II receptor type 1 (AT1 R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease.}, keywords = {Oxygen, TR57Y}, pubstate = {published}, tppubtype = {article} } KEY POINTS: Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease.
ABSTRACT: We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min-1 . Equi-pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin-angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PO2. This could be reversed within minutes by pharmacological angiotensin-II receptor type 1 (AT1 R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease. |
2015 |
|
dela Pena, I J; Hong, E; de la Pena, J B; Kim, H J; Botanas, C J; Hong, Y S; Hwang, Y S; Moon, B S; Cheong, J H Milk Collected at Night Induces Sedative and Anxiolytic-Like Effects and Augments Pentobarbital-Induced Sleeping Behavior in Mice Journal Article Journal of medicinal food, 18 (11), pp. 1255-1261, 2015, ISBN: 1557-7600. Abstract | Links | BibTeX | Tags: EEG, Rat, TR50B @article{RefWorks:doc:5c74bbd2e4b02df9431d7f7d,
title = {Milk Collected at Night Induces Sedative and Anxiolytic-Like Effects and Augments Pentobarbital-Induced Sleeping Behavior in Mice}, author = {I J dela Pena and E Hong and J B de la Pena and H J Kim and C J Botanas and Y S Hong and Y S Hwang and B S Moon and J H Cheong}, doi = {10.1089/jmf.2015.3448}, isbn = {1557-7600}, year = {2015}, date = {2015-11-01}, journal = {Journal of medicinal food}, volume = {18}, number = {11}, pages = {1255-1261}, abstract = {Milk has long been known and used to promote sleep. The sleep-promoting effect of milk has been attributed to its psychological associations (i.e., the memory of a mother giving milk at bedtime) and its rich store of sleep-promoting constituents (e.g., tryptophan). Studies have shown that milk harvested at night (Night milk) contains exceptionally high amounts of tryptophan and melatonin. In the present study, we evaluated the psychopharmacological properties of Night milk, particularly its probable sleep-promoting/enhancing, and anxiolytic effects. Night milk was orally administered to ICR mice at various concentrations (100, 200, or 300 mg/kg). An hour after administration, assessment of its sedative (open-field and rotarod tests) and sedative sleep-potentiating effects (pentobarbital-induced sleeping test) was conducted. For comparison, the effects of Day milk (daytime milking) were also assessed. In addition, the effects of Night milk on anxiety behavior (elevated plus maze [EPM] test) and electroencephalographic (EEG) waves were evaluated. Night milk-treated animals exhibited decreased spontaneous locomotion (open-field test) and impaired motor balance and coordination (rotarod test). Furthermore, Night milk shortened the sleep onset and prolonged the sleep duration induced by pentobarbital sodium. These effects were comparable to that of diazepam. In addition, Night milk significantly increased the percentage of time spent and entries into the open arms of the EPM, indicating that it also has anxiolytic effects. No significant changes in EEG waves were observed. Altogether, these findings suggest that Night milk is a promising natural aid for sleep- and anxiety-related disturbances.}, keywords = {EEG, Rat, TR50B}, pubstate = {published}, tppubtype = {article} } Milk has long been known and used to promote sleep. The sleep-promoting effect of milk has been attributed to its psychological associations (i.e., the memory of a mother giving milk at bedtime) and its rich store of sleep-promoting constituents (e.g., tryptophan). Studies have shown that milk harvested at night (Night milk) contains exceptionally high amounts of tryptophan and melatonin. In the present study, we evaluated the psychopharmacological properties of Night milk, particularly its probable sleep-promoting/enhancing, and anxiolytic effects. Night milk was orally administered to ICR mice at various concentrations (100, 200, or 300 mg/kg). An hour after administration, assessment of its sedative (open-field and rotarod tests) and sedative sleep-potentiating effects (pentobarbital-induced sleeping test) was conducted. For comparison, the effects of Day milk (daytime milking) were also assessed. In addition, the effects of Night milk on anxiety behavior (elevated plus maze [EPM] test) and electroencephalographic (EEG) waves were evaluated. Night milk-treated animals exhibited decreased spontaneous locomotion (open-field test) and impaired motor balance and coordination (rotarod test). Furthermore, Night milk shortened the sleep onset and prolonged the sleep duration induced by pentobarbital sodium. These effects were comparable to that of diazepam. In addition, Night milk significantly increased the percentage of time spent and entries into the open arms of the EPM, indicating that it also has anxiolytic effects. No significant changes in EEG waves were observed. Altogether, these findings suggest that Night milk is a promising natural aid for sleep- and anxiety-related disturbances.
|
|
Read, M I; Harrison, J C; Kerr, D S; Sammut, I A Atenolol offers better protection than clonidine against cardiac injury in kainic acid-induced status epilepticus Journal Article British journal of pharmacology, 172 (19), pp. 4626-4638, 2015, ISBN: 1476-5381. Abstract | Links | BibTeX | Tags: ECG, EEG, Rat, TR50BB @article{RefWorks:doc:5c74bdd7e4b073ca706afcf3,
title = {Atenolol offers better protection than clonidine against cardiac injury in kainic acid-induced status epilepticus}, author = {M I Read and J C Harrison and D S Kerr and I A Sammut}, doi = {10.1111/bph.13132}, isbn = {1476-5381}, year = {2015}, date = {2015-10-01}, journal = {British journal of pharmacology}, volume = {172}, number = {19}, pages = {4626-4638}, abstract = {BACKGROUND AND PURPOSE: Status epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology. EXPERIMENTAL APPROACH: Sprague-Dawley rats (male, 300-350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA-induced seizures. Animals were randomized into saline controls, and saline vehicle-, clonidine- or atenolol-pretreated KA groups. KEY RESULTS: KA administration in the saline-pretreated group produced an immediate bradycardic response (maximal decrease of 28 +/- 6%), coinciding with low-level seizure activity. As high-level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 +/- 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA-induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline-KA group. CONCLUSIONS AND IMPLICATIONS: Severe seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus.}, keywords = {ECG, EEG, Rat, TR50BB}, pubstate = {published}, tppubtype = {article} } BACKGROUND AND PURPOSE: Status epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology. EXPERIMENTAL APPROACH: Sprague-Dawley rats (male, 300-350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA-induced seizures. Animals were randomized into saline controls, and saline vehicle-, clonidine- or atenolol-pretreated KA groups. KEY RESULTS: KA administration in the saline-pretreated group produced an immediate bradycardic response (maximal decrease of 28 +/- 6%), coinciding with low-level seizure activity. As high-level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 +/- 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA-induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline-KA group. CONCLUSIONS AND IMPLICATIONS: Severe seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus.
|
|
Sarah-Jane Guild Fiona D. McBryde, Simon Malpas C Recording of intracranial pressure in conscious rats via telemetry. Journal Article Journal of Applied Physiology, 119 (5), pp. 576-581, 2015. Abstract | Links | BibTeX | Tags: Blood Pressure, Intracranial Pressure, Rat, TRM54PP2509 @article{Guild2015,
title = {Recording of intracranial pressure in conscious rats via telemetry.}, author = {Sarah-Jane Guild, Fiona D. McBryde, Simon C. Malpas}, doi = {10.1152/japplphysiol.00165.2015}, year = {2015}, date = {2015-09-01}, journal = {Journal of Applied Physiology}, volume = {119}, number = {5}, pages = {576-581}, abstract = {Although cerebral perfusion pressure (CPP) is known to be fundamental in the control of normal brain function, there have been no previous long-term measurements in animal models. The aim of this study was to explore the stability and viability of long-term recordings of intracranial pressure (ICP) in freely moving rats via a telemetry device. We also developed a repeatable surgical approach with a solid-state pressure sensor at the tip of the catheter placed under the dura and in combination with arterial pressure (AP) measurement to enable the calculation of CPP. Telemeters with dual pressure catheters were implanted in Wistar rats to measure ICP and AP. We found that the signals were stable throughout the 28-day recording period with an average ICP value of 6 ± 0.8 mmHg. Significant light-dark differences were found in AP (3.1 ± 2.7 mmHg, P = 0.02) and HR (58 ± 12 beats/min, P = 0.003), but not ICP (0.3 ± 0.2 mmHg, P >0.05) or CPP (2.6 ± 2.8 mmHg, P > 0.05). Use of kaolin to induce hydrocephalus in several rats demonstrates the ability to measure changes in ICP throughout disease progression, validating this new solution for chronic measurement of ICP, CPP, and AP in conscious rats.}, keywords = {Blood Pressure, Intracranial Pressure, Rat, TRM54PP2509}, pubstate = {published}, tppubtype = {article} } Although cerebral perfusion pressure (CPP) is known to be fundamental in the control of normal brain function, there have been no previous long-term measurements in animal models. The aim of this study was to explore the stability and viability of long-term recordings of intracranial pressure (ICP) in freely moving rats via a telemetry device. We also developed a repeatable surgical approach with a solid-state pressure sensor at the tip of the catheter placed under the dura and in combination with arterial pressure (AP) measurement to enable the calculation of CPP. Telemeters with dual pressure catheters were implanted in Wistar rats to measure ICP and AP. We found that the signals were stable throughout the 28-day recording period with an average ICP value of 6 ± 0.8 mmHg. Significant light-dark differences were found in AP (3.1 ± 2.7 mmHg, P = 0.02) and HR (58 ± 12 beats/min, P = 0.003), but not ICP (0.3 ± 0.2 mmHg, P >0.05) or CPP (2.6 ± 2.8 mmHg, P > 0.05). Use of kaolin to induce hydrocephalus in several rats demonstrates the ability to measure changes in ICP throughout disease progression, validating this new solution for chronic measurement of ICP, CPP, and AP in conscious rats.
|
|
Jeon, S J; Park, H J; Gao, Q; Pena, I J; Park, S J; Lee, H E; Woo, H; Kim, H J; Cheong, J H; Hong, E; Ryu, J H Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice Journal Article European journal of pharmacology, 762 , pp. 443-448, 2015, ISBN: 1879-0712. Abstract | Links | BibTeX | Tags: EEG, Rat, TR50B @article{RefWorks:doc:5c74bc89e4b0947789161361,
title = {Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice}, author = {S J Jeon and H J Park and Q Gao and I J Pena and S J Park and H E Lee and H Woo and H J Kim and J H Cheong and E Hong and J H Ryu}, doi = {10.1016/j.ejphar.2015.06.037}, isbn = {1879-0712}, year = {2015}, date = {2015-09-01}, journal = {European journal of pharmacology}, volume = {762}, pages = {443-448}, abstract = {Prunella vulgaris is widely used as a herbal medicine for cancers, inflammatory diseases, and other infections. Although it has long been used, few studies have examined its effects on central nervous system function. Here, we first observed that ethanolic extracts of P. vulgaris (EEPV) prolonged pentobarbital-induced sleep duration in mice. It is known that EEPV consists of many active components including triterpenoid (ursolic acid and oleanolic acid), which have many biological activities. Therefore, we evaluated which EEPV components induced sleep extension in pentobarbital-mediated sleeping model in mice. Surprisingly, despite their structural similarity and other common functions such as anti-inflammation, anti-cancer, and tissue protection, only ursolic acid enhanced sleep duration in pentobarbital-treated mice. These results were attenuated by bicuculline treatment, which is a GABAA receptor antagonist. The present results suggest that ursolic acid from P. vulgaris enhances sleep duration through GABAA receptor activation and could be a therapeutic candidate for insomnia treatment.}, keywords = {EEG, Rat, TR50B}, pubstate = {published}, tppubtype = {article} } Prunella vulgaris is widely used as a herbal medicine for cancers, inflammatory diseases, and other infections. Although it has long been used, few studies have examined its effects on central nervous system function. Here, we first observed that ethanolic extracts of P. vulgaris (EEPV) prolonged pentobarbital-induced sleep duration in mice. It is known that EEPV consists of many active components including triterpenoid (ursolic acid and oleanolic acid), which have many biological activities. Therefore, we evaluated which EEPV components induced sleep extension in pentobarbital-mediated sleeping model in mice. Surprisingly, despite their structural similarity and other common functions such as anti-inflammation, anti-cancer, and tissue protection, only ursolic acid enhanced sleep duration in pentobarbital-treated mice. These results were attenuated by bicuculline treatment, which is a GABAA receptor antagonist. The present results suggest that ursolic acid from P. vulgaris enhances sleep duration through GABAA receptor activation and could be a therapeutic candidate for insomnia treatment.
|
|
Salman, I M; Kandukuri, Sarma D; Harrison, J L; Hildreth, C M; Phillips, J K Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease Journal Article Frontiers in physiology, 6 , pp. 218, 2015, ISBN: 1664-042X. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TRM56SP @article{RefWorks:doc:5c0dc3b5e4b0fec09b0a6cdc,
title = {Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease}, author = {I M Salman and Sarma D Kandukuri and J L Harrison and C M Hildreth and J K Phillips}, doi = {10.3389/fphys.2015.00218}, isbn = {1664-042X}, year = {2015}, date = {2015-08-01}, journal = {Frontiers in physiology}, volume = {6}, pages = {218}, abstract = {Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n = 16) were instrumented for telemetric recording of RSNA and MAP. At 12-13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2) and central chemoreflex (hypercapnia: 7% CO2) activation and acute stress (open-field exposure), were measured. As indicators of renal function, urinary protein (UPro) and creatinine (UCr) levels were assessed. LPK rats had higher resting RSNA (1.2 +/- 0.1 vs. 0.6 +/- 0.1 muV, p < 0.05) and MAP (151 +/- 8 vs. 97 +/- 2 mmHg, p < 0.05) compared to Lewis. MAP was negatively correlated with UCr (r = -0.80}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TRM56SP}, pubstate = {published}, tppubtype = {article} } Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n = 16) were instrumented for telemetric recording of RSNA and MAP. At 12-13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2) and central chemoreflex (hypercapnia: 7% CO2) activation and acute stress (open-field exposure), were measured. As indicators of renal function, urinary protein (UPro) and creatinine (UCr) levels were assessed. LPK rats had higher resting RSNA (1.2 +/- 0.1 vs. 0.6 +/- 0.1 muV, p < 0.05) and MAP (151 +/- 8 vs. 97 +/- 2 mmHg, p < 0.05) compared to Lewis. MAP was negatively correlated with UCr (r = -0.80
|
|
Mendes-Junior, Ld; Guimaraes, D D; Gadelha, D D; Diniz, T F; Brandao, M C; Athayde-Filho, P F; Lemos, V S; Mdo, Franca-Silva S; Braga, V A The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway Journal Article Frontiers in physiology, 6 , pp. 243, 2015, ISBN: 1664-042X. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM54P @article{RefWorks:doc:5c74bd89e4b0b01390453cf4,
title = {The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway}, author = {Ld Mendes-Junior and D D Guimaraes and D D Gadelha and T F Diniz and M C Brandao and P F Athayde-Filho and V S Lemos and Franca-Silva S Mdo and V A Braga}, doi = {10.3389/fphys.2015.00243}, isbn = {1664-042X}, year = {2015}, date = {2015-08-01}, journal = {Frontiers in physiology}, volume = {6}, pages = {243}, abstract = {We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 +/- 4.1%; potency [pD2] = 5.1 +/- 0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9 +/- 9.4% vs. 100.4 +/- 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 +/- 9.7% vs. 100.4 +/- 4.1%). In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 +/- 0.1 vs. 5.1 +/- 0.1) or by inhibiting KATP channels (pD2 = 4.3 +/- 0.1 vs. 5.1 +/- 0.1). HEX increased NO levels in mesenteric arteries (33.2 +/- 2.3 vs. 10.7 +/- 0.2 au, p < 0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 +/- 6 vs. 170 +/- 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K(+) channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.}, keywords = {Blood Pressure, Rat, TRM54P}, pubstate = {published}, tppubtype = {article} } We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 +/- 4.1%; potency [pD2] = 5.1 +/- 0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9 +/- 9.4% vs. 100.4 +/- 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 +/- 9.7% vs. 100.4 +/- 4.1%). In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 +/- 0.1 vs. 5.1 +/- 0.1) or by inhibiting KATP channels (pD2 = 4.3 +/- 0.1 vs. 5.1 +/- 0.1). HEX increased NO levels in mesenteric arteries (33.2 +/- 2.3 vs. 10.7 +/- 0.2 au, p < 0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 +/- 6 vs. 170 +/- 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K(+) channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.
|
|
Pinkham, M I; Whalley, G A; Guild, S J; Malpas, S C; Barrett, C J American journal of physiology.Regulatory, integrative and comparative physiology, 309 (2), pp. 169, 2015, ISBN: 1522-1490. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c74bdaee4b05c2b63540bcc,
title = {Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats}, author = {M I Pinkham and G A Whalley and S J Guild and S C Malpas and C J Barrett}, doi = {10.1152/ajpregu.00026.2015}, isbn = {1522-1490}, year = {2015}, date = {2015-07-01}, journal = {American journal of physiology.Regulatory, integrative and comparative physiology}, volume = {309}, number = {2}, pages = {169}, abstract = {There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 +/- 6 vs. 84 +/- 5% in male sham group) and OVX large MI group (37 +/- 3 vs. 75 +/- 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 +/- 6 vs. 84 +/- 5% in male sham group) and OVX large MI group (37 +/- 3 vs. 75 +/- 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI.
|
|
Pinkham, M I; Barrett, C J Estradiol alters the chemosensitive cardiac afferent reflex in female rats by augmenting sympathoinhibition and attenuating sympathoexcitation Journal Article Clinical and experimental pharmacology & physiology, 42 (6), pp. 622-631, 2015, ISBN: 1440-1681. Abstract | Links | BibTeX | Tags: Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c74bdaee4b05c2b63540bcd,
title = {Estradiol alters the chemosensitive cardiac afferent reflex in female rats by augmenting sympathoinhibition and attenuating sympathoexcitation}, author = {M I Pinkham and C J Barrett}, doi = {10.1111/1440-1681.12392}, isbn = {1440-1681}, year = {2015}, date = {2015-06-01}, journal = {Clinical and experimental pharmacology & physiology}, volume = {42}, number = {6}, pages = {622-631}, abstract = {The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were performed in anaesthetized, sinoaortic baroreceptor denervated male, female and ovariectomized female (OVX) Wistar rats with either intact cardiac innervation or bilateral vagotomy. To investigate the chemosensitive cardiac afferent reflexes renal SNA, heart rate (HR) and arterial pressure (AP) were recorded before and following application of capsaicin onto the epicardial surface of the left ventricle. Compared to males, ovary-intact females displayed similar cardiac afferent reflex mediated changes in renal SNA albeit with a reduced maximum sympathetic reflex driven increase in renal SNA. In females, ovariectomy significantly attenuated the cardiac vagal afferent reflex mediated inhibition of renal SNA (renal SNA decreased 2 +/- 17% in OVX versus -50 +/- 4% in ovary-intact females, P < 0.05) and augmented cardiac sympathetic afferent reflex mediated sympathoexcitation (renal SNA increased 91 +/- 11% in OVX vs 62 +/- 9% in ovary-intact females, P < 0.05) so that overall increases in reflex driven sympathoexcitation were significantly enhanced. Chronic estradiol replacement, but not progesterone replacement, begun at time of ovariectomy restored cardiac afferent reflex responses to be similar as ovary-intact females. Vagal denervation eliminated all group differences. The current findings show ovariectomy in female rats, mimicking menopause in women, results in greater chemosensitive cardiac afferent reflex driven sympathoexcitation and does so, at least partly, via the loss of estradiols actions on the cardiac vagal afferent reflex pathway.}, keywords = {Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were performed in anaesthetized, sinoaortic baroreceptor denervated male, female and ovariectomized female (OVX) Wistar rats with either intact cardiac innervation or bilateral vagotomy. To investigate the chemosensitive cardiac afferent reflexes renal SNA, heart rate (HR) and arterial pressure (AP) were recorded before and following application of capsaicin onto the epicardial surface of the left ventricle. Compared to males, ovary-intact females displayed similar cardiac afferent reflex mediated changes in renal SNA albeit with a reduced maximum sympathetic reflex driven increase in renal SNA. In females, ovariectomy significantly attenuated the cardiac vagal afferent reflex mediated inhibition of renal SNA (renal SNA decreased 2 +/- 17% in OVX versus -50 +/- 4% in ovary-intact females, P < 0.05) and augmented cardiac sympathetic afferent reflex mediated sympathoexcitation (renal SNA increased 91 +/- 11% in OVX vs 62 +/- 9% in ovary-intact females, P < 0.05) so that overall increases in reflex driven sympathoexcitation were significantly enhanced. Chronic estradiol replacement, but not progesterone replacement, begun at time of ovariectomy restored cardiac afferent reflex responses to be similar as ovary-intact females. Vagal denervation eliminated all group differences. The current findings show ovariectomy in female rats, mimicking menopause in women, results in greater chemosensitive cardiac afferent reflex driven sympathoexcitation and does so, at least partly, via the loss of estradiols actions on the cardiac vagal afferent reflex pathway.
|
|
dela Pena, I J; Hong, E; Kim, H J; de la Pena, J B; Woo, T S; Lee, Y S; Cheong, J H Artemisia capillaris Thunberg Produces Sedative-Hypnotic Effects in Mice, Which are Probably Mediated Through Potentiation of the GABAA Receptor Journal Article The American Journal of Chinese Medicine, 43 (4), pp. 667-679, 2015, ISBN: 1793-6853. Abstract | Links | BibTeX | Tags: EEG, Rat, TR50B @article{RefWorks:doc:5c74bc23e4b0b01390453cde,
title = {Artemisia capillaris Thunberg Produces Sedative-Hypnotic Effects in Mice, Which are Probably Mediated Through Potentiation of the GABAA Receptor}, author = {I J dela Pena and E Hong and H J Kim and J B de la Pena and T S Woo and Y S Lee and J H Cheong}, doi = {10.1142/S0192415X1550041X}, isbn = {1793-6853}, year = {2015}, date = {2015-01-01}, journal = {The American Journal of Chinese Medicine}, volume = {43}, number = {4}, pages = {667-679}, abstract = {The Artemisia group of plants has long been used as a traditional remedy for various conditions. The present study assessed the sleep-promoting (sedative-hypnotic) effects of Artemisia capillaris Thunberg (A. capillaris), and elucidated a possible mechanism behind its effect. ICR mice were given A. capillaris extract (oral) at different dosages (50, 100, 200, 300, or 400 mg/kg), distilled water (oral; control), or diazepam (intraperitoneal; reference drug). One hour after administration, locomotion (open-field test) and motor coordination (rota-rod test) were assessed. The extract's effect on pentobarbital-induced sleep was also evaluated. Additionally, electroencephalographic (EEG) recordings were measured in rats. To evaluate a possible mechanism behind its effects, changes in chloride ( Cl (-)) ion influx were measured in human neuroblastoma cells. As compared to the control group, mice treated with A. capillaris demonstrated significantly decreased locomotor activity and impaired motor balance and coordination. The extract also shortened the onset and lengthened the duration of sleep induced by pentobarbital sodium. These effects were comparable to that induced by diazepam. Furthermore, A. capillaris-treated rats showed increased delta and decreased alpha EEG waves; an electroencephalographic pattern indicative of relaxation or sedation. In neuroblastoma cells, the extract dose-dependently increased Cl (-) ion influx, which was blocked by co-administration of bicuculline, a GABAA receptor competitive antagonist, suggesting that its effects are mediated through the GABAA receptor- Cl (-) ion channel complex. Altogether, the results of the present study demonstrate that A. capillaris possesses potent sedative-hypnotic effects, which are probably mediated through potentiation of the GABAA receptor- Cl (-) ion channel complex.}, keywords = {EEG, Rat, TR50B}, pubstate = {published}, tppubtype = {article} } The Artemisia group of plants has long been used as a traditional remedy for various conditions. The present study assessed the sleep-promoting (sedative-hypnotic) effects of Artemisia capillaris Thunberg (A. capillaris), and elucidated a possible mechanism behind its effect. ICR mice were given A. capillaris extract (oral) at different dosages (50, 100, 200, 300, or 400 mg/kg), distilled water (oral; control), or diazepam (intraperitoneal; reference drug). One hour after administration, locomotion (open-field test) and motor coordination (rota-rod test) were assessed. The extract's effect on pentobarbital-induced sleep was also evaluated. Additionally, electroencephalographic (EEG) recordings were measured in rats. To evaluate a possible mechanism behind its effects, changes in chloride ( Cl (-)) ion influx were measured in human neuroblastoma cells. As compared to the control group, mice treated with A. capillaris demonstrated significantly decreased locomotor activity and impaired motor balance and coordination. The extract also shortened the onset and lengthened the duration of sleep induced by pentobarbital sodium. These effects were comparable to that induced by diazepam. Furthermore, A. capillaris-treated rats showed increased delta and decreased alpha EEG waves; an electroencephalographic pattern indicative of relaxation or sedation. In neuroblastoma cells, the extract dose-dependently increased Cl (-) ion influx, which was blocked by co-administration of bicuculline, a GABAA receptor competitive antagonist, suggesting that its effects are mediated through the GABAA receptor- Cl (-) ion channel complex. Altogether, the results of the present study demonstrate that A. capillaris possesses potent sedative-hypnotic effects, which are probably mediated through potentiation of the GABAA receptor- Cl (-) ion channel complex.
|
2014 |
|
Bussey, C T; de Leeuw, A E; Lamberts, R R Increased haemodynamic adrenergic load with isoflurane anaesthesia in type 2 diabetic and obese rats in vivo Journal Article Cardiovascular diabetology, 13 , pp. 4, 2014, ISBN: 1475-2840. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM53P @article{RefWorks:doc:5c74a822e4b083cef79d1cb3,
title = {Increased haemodynamic adrenergic load with isoflurane anaesthesia in type 2 diabetic and obese rats in vivo}, author = {C T Bussey and A E de Leeuw and R R Lamberts}, doi = {10.1186/s12933-014-0161-4}, isbn = {1475-2840}, year = {2014}, date = {2014-12-01}, journal = {Cardiovascular diabetology}, volume = {13}, pages = {4}, abstract = {BACKGROUND: Increasing numbers of type 2 diabetic and obese patients with enhanced rates of cardiovascular complications require surgical interventions, however they have a higher incidence of perioperative haemodynamic complications, which has been linked to adrenergic dysfunction. Therefore, we aimed to determine how alpha- and beta-adrenoceptor (AR)-mediated haemodynamic responses are affected by isoflurane anaesthesia in experimental type 2 diabetes and obesity in vivo. METHODS: Sixteen-week old male Zucker type 2 Diabetic Fatty (ZDF) rats, Zucker Obese rats and their lean counterparts (n = 7-9 per group) were instrumented with radio telemeters to record blood pressure and heart rate and with vascular access ports for non-invasive intravenous drug delivery in vivo. Haemodynamic effects of alpha-AR (phenylephrine; 1-100 mug x kg(-1)) or beta-AR (dobutamine; 2-120 mug x kg(-1)) stimulation were assessed under conscious and anaesthetised (isoflurane; 2%) conditions. RESULTS: Vascular alpha-AR sensitivity was increased in both diabetic (non-diabetic 80 +/- 3 vs. diabetic 95 +/- 4 DeltammHg at 100 mug x kg(-1); p < 0.05) and obese (lean 65 +/- 6 vs. obese 84 +/- 6 DeltammHg at 20 mug x kg(-1); p < 0.05) conscious rats. Interestingly, anaesthesia exacerbated and prolonged the increased alpha-AR function in both diabetic and obese animals (non-diabetic 51 +/- 1 vs. diabetic 68 +/- 4 DeltammHg, lean 61 +/- 5 vs. obese 84 +/- 2 DeltammHg at 20 mug x kg(-1); p < 0.05). Meanwhile, beta-AR chronotropic sensitivity was reduced in conscious diabetic and obese rats (non-diabetic 58 +/- 7 vs. diabetic 27 +/- 8 Deltabpm, lean 103 +/- 12 vs. obese 61 +/- 9 Deltabpm at 15 mug x kg(-1); p < 0.05). Anaesthesia normalised chronotropic beta-AR responses, via either a limited reduction in obese (lean 51 +/- 3 vs. obese 66 +/- 5 Deltabpm; NS at 15 mug x kg(-1)) or increased responses in diabetic animals (non-diabetic 49 +/- 8 vs. diabetic 63 +/- 8 Deltabpm, at 15 mug x kg(-1); NS at 15 mug x kg(-1)). CONCLUSIONS: Long term metabolic stress, such as during type 2 diabetes and obesity, alters alpha- and beta-AR function, its dynamics and the interaction with isoflurane anaesthesia. During anaesthesia, enhanced alpha-AR sensitivity and normalised beta-AR function may impair cardiovascular function in experimental type 2 diabetes and obesity.}, keywords = {Blood Pressure, Rat, TRM53P}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Increasing numbers of type 2 diabetic and obese patients with enhanced rates of cardiovascular complications require surgical interventions, however they have a higher incidence of perioperative haemodynamic complications, which has been linked to adrenergic dysfunction. Therefore, we aimed to determine how alpha- and beta-adrenoceptor (AR)-mediated haemodynamic responses are affected by isoflurane anaesthesia in experimental type 2 diabetes and obesity in vivo. METHODS: Sixteen-week old male Zucker type 2 Diabetic Fatty (ZDF) rats, Zucker Obese rats and their lean counterparts (n = 7-9 per group) were instrumented with radio telemeters to record blood pressure and heart rate and with vascular access ports for non-invasive intravenous drug delivery in vivo. Haemodynamic effects of alpha-AR (phenylephrine; 1-100 mug x kg(-1)) or beta-AR (dobutamine; 2-120 mug x kg(-1)) stimulation were assessed under conscious and anaesthetised (isoflurane; 2%) conditions. RESULTS: Vascular alpha-AR sensitivity was increased in both diabetic (non-diabetic 80 +/- 3 vs. diabetic 95 +/- 4 DeltammHg at 100 mug x kg(-1); p < 0.05) and obese (lean 65 +/- 6 vs. obese 84 +/- 6 DeltammHg at 20 mug x kg(-1); p < 0.05) conscious rats. Interestingly, anaesthesia exacerbated and prolonged the increased alpha-AR function in both diabetic and obese animals (non-diabetic 51 +/- 1 vs. diabetic 68 +/- 4 DeltammHg, lean 61 +/- 5 vs. obese 84 +/- 2 DeltammHg at 20 mug x kg(-1); p < 0.05). Meanwhile, beta-AR chronotropic sensitivity was reduced in conscious diabetic and obese rats (non-diabetic 58 +/- 7 vs. diabetic 27 +/- 8 Deltabpm, lean 103 +/- 12 vs. obese 61 +/- 9 Deltabpm at 15 mug x kg(-1); p < 0.05). Anaesthesia normalised chronotropic beta-AR responses, via either a limited reduction in obese (lean 51 +/- 3 vs. obese 66 +/- 5 Deltabpm; NS at 15 mug x kg(-1)) or increased responses in diabetic animals (non-diabetic 49 +/- 8 vs. diabetic 63 +/- 8 Deltabpm, at 15 mug x kg(-1); NS at 15 mug x kg(-1)). CONCLUSIONS: Long term metabolic stress, such as during type 2 diabetes and obesity, alters alpha- and beta-AR function, its dynamics and the interaction with isoflurane anaesthesia. During anaesthesia, enhanced alpha-AR sensitivity and normalised beta-AR function may impair cardiovascular function in experimental type 2 diabetes and obesity.
|
|
Bussey, C T; Leeuw, A E; Cook, R F; Ashley, Z; Schofield, J; Lamberts, R R Laboratory animals, 48 (3), pp. 250-260, 2014, ISBN: 1758-1117. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM53P @article{RefWorks:doc:5c74a7b5e4b094778916104f,
title = {Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats}, author = {C T Bussey and A E Leeuw and R F Cook and Z Ashley and J Schofield and R R Lamberts}, url = {https://journals.sagepub.com/doi/10.1177/0023677214530687}, isbn = {1758-1117}, year = {2014}, date = {2014-07-01}, journal = {Laboratory animals}, volume = {48}, number = {3}, pages = {250-260}, abstract = {Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 microg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the beta-adrenoceptor agonist dobutamine (30 microg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions.}, keywords = {Blood Pressure, Rat, TRM53P}, pubstate = {published}, tppubtype = {article} } Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 microg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the beta-adrenoceptor agonist dobutamine (30 microg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions.
|
|
Medarametla, V; Festin, S; Sugarragchaa, C; Eng, A; Naqwi, A; Wiedmann, T; Zisman, L S PK10453, a nonselective platelet-derived growth factor receptor inhibitor, prevents the progression of pulmonary arterial hypertension Journal Article Pulmonary circulation, 4 (1), pp. 82-102, 2014, ISBN: 2045-8932. Abstract | Links | BibTeX | Tags: Pulmonary artery pressure, Rat, TRM53P @article{RefWorks:doc:5c74aa8de4b02df9431d7dce,
title = {PK10453, a nonselective platelet-derived growth factor receptor inhibitor, prevents the progression of pulmonary arterial hypertension}, author = {V Medarametla and S Festin and C Sugarragchaa and A Eng and A Naqwi and T Wiedmann and L S Zisman}, doi = {10.1086/674881}, isbn = {2045-8932}, year = {2014}, date = {2014-03-01}, journal = {Pulmonary circulation}, volume = {4}, number = {1}, pages = {82-102}, abstract = {The platelet-derived growth factor (PDGF) signaling pathway has been found to be activated in human pulmonary arterial hypertension (PAH) and in animal models of the disease. Our study tested the hypothesis that a novel, nonselective inhaled PDGF receptor inhibitor, PK10453, would decrease pulmonary hypertension both in the rat monocrotaline (MCT) model and the rat MCT plus pneumonectomy (MCT+PN) model of PAH. PK10453, delivered by inhalation for 4 (D4)- and 8 (D8)-minute exposures 3 times a day for 2 weeks, decreased right ventricular systolic pressure (RVSP) in both the rat MCT and rat MCT+PN models: RVSP was 80.4 +/- 2.6 mmHg in the vehicle MCT group (n = 6), 44.4 +/- 5.8 mmHg in the D4 MCT group (n = 6), and 37.1 +/- 4.5 mmHg in the D8 MCT group (n = 5; P < 0.001 vs. vehicle); RVSP was 75.7 +/- 7.1 mmHg in the vehicle MCT+PN group (n = 9), 40.4 +/- 2.7 mmHg in the D4 MCT+PN group (n = 10), and 43.0 +/- 3.0 mmHg in the D8 MCT+PN group (n = 8; P < 0.001). In the rat MCT+PN model, continuous telemetry monitoring of pulmonary artery pressures also demonstrated that PK10453 prevented the progression of PAH. Imatinib given by inhalation was equally effective in the MCT model but was not effective in the MCT+PN model. Immunohistochemistry demonstrated increased activation of the PDGFbeta receptor compared to the PDGFalpha receptor in neointimal and perivascular lesions found in the MCT+PN model. We show that imatinib is selective for the PDGFalpha receptor, whereas PK10453 has a lower half-maximal inhibitor concentration (IC50) for inhibition of kinase activity of both the PDGFalpha and PDGFbeta receptors compared to imatinib. In conclusion, PK10453, when delivered by inhalation, significantly decreased the progression of PAH in the rat MCT and MCT+PN models. Nonselective inhibition of both the PDGFalpha and PDGFbeta receptors may have a therapeutic advantage over selective PDGFalpha receptor inhibition in PAH.}, keywords = {Pulmonary artery pressure, Rat, TRM53P}, pubstate = {published}, tppubtype = {article} } The platelet-derived growth factor (PDGF) signaling pathway has been found to be activated in human pulmonary arterial hypertension (PAH) and in animal models of the disease. Our study tested the hypothesis that a novel, nonselective inhaled PDGF receptor inhibitor, PK10453, would decrease pulmonary hypertension both in the rat monocrotaline (MCT) model and the rat MCT plus pneumonectomy (MCT+PN) model of PAH. PK10453, delivered by inhalation for 4 (D4)- and 8 (D8)-minute exposures 3 times a day for 2 weeks, decreased right ventricular systolic pressure (RVSP) in both the rat MCT and rat MCT+PN models: RVSP was 80.4 +/- 2.6 mmHg in the vehicle MCT group (n = 6), 44.4 +/- 5.8 mmHg in the D4 MCT group (n = 6), and 37.1 +/- 4.5 mmHg in the D8 MCT group (n = 5; P < 0.001 vs. vehicle); RVSP was 75.7 +/- 7.1 mmHg in the vehicle MCT+PN group (n = 9), 40.4 +/- 2.7 mmHg in the D4 MCT+PN group (n = 10), and 43.0 +/- 3.0 mmHg in the D8 MCT+PN group (n = 8; P < 0.001). In the rat MCT+PN model, continuous telemetry monitoring of pulmonary artery pressures also demonstrated that PK10453 prevented the progression of PAH. Imatinib given by inhalation was equally effective in the MCT model but was not effective in the MCT+PN model. Immunohistochemistry demonstrated increased activation of the PDGFbeta receptor compared to the PDGFalpha receptor in neointimal and perivascular lesions found in the MCT+PN model. We show that imatinib is selective for the PDGFalpha receptor, whereas PK10453 has a lower half-maximal inhibitor concentration (IC50) for inhibition of kinase activity of both the PDGFalpha and PDGFbeta receptors compared to imatinib. In conclusion, PK10453, when delivered by inhalation, significantly decreased the progression of PAH in the rat MCT and MCT+PN models. Nonselective inhibition of both the PDGFalpha and PDGFbeta receptors may have a therapeutic advantage over selective PDGFalpha receptor inhibition in PAH.
|
|
Li, D P; Zhu, L H; Pachuau, J; Lee, H A; Pan, H L The Journal of neuroscience : the official journal of the Society for Neuroscience, 34 (12), pp. 4309-4317, 2014, ISBN: 1529-2401. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM54P @article{RefWorks:doc:5c74a9c9e4b0061ca5b6bb91,
title = {mGluR5 Upregulation increases excitability of hypothalamic presympathetic neurons through NMDA receptor trafficking in spontaneously hypertensive rats}, author = {D P Li and L H Zhu and J Pachuau and H A Lee and H L Pan}, doi = {10.1523/JNEUROSCI.4295-13.2014}, isbn = {1529-2401}, year = {2014}, date = {2014-03-01}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {34}, number = {12}, pages = {4309-4317}, abstract = {The hypothalamic paraventricular nucleus (PVN) is critically involved in elevated sympathetic output and the development of hypertension. However, changes in group I metabotropic glutamate receptors (mGluR1 and mGluR5) and their relevance to the hyperactivity of PVN presympathetic neurons in hypertension remain unclear. Here, we found that selectively blocking mGluR5 significantly reduced the basal firing activity of spinally projecting PVN neurons in spontaneously hypertensive rats (SHRs), but not in normotensive Wistar-Kyoto (WKY) rats. However, blocking mGluR1 had no effect on the firing activity of PVN neurons in either group. The mRNA and protein levels of mGluR5 in the PVN and rostral ventrolateral medulla were significantly higher in SHRs than in WKY rats. The group I mGluR selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) similarly increased the firing activity of PVN neurons in WKY rats and SHRs. In addition, blocking NMDA receptors (NMDARs) through bath application or intracellular dialysis not only decreased the basal firing in SHRs, but also eliminated DHPG-induced excitation of spinally projecting PVN neurons. DHPG significantly increased the amplitude of NMDAR currents without changing their decay kinetics. Interestingly, DHPG still increased the amplitude of NMDAR currents and caused reappearance of functional NMDAR channels after initially blocking NMDARs. In addition, protein kinase C (PKC) inhibition or intracellular dialysis with synaptosomal-associated protein of 25 kDa (SNAP-25)-blocking peptide abolished DHPG-induced increases in NMDAR currents of PVN neurons in SHRs. Our findings suggest that mGluR5 in the PVN is upregulated in hypertension and contributes to the hyperactivity of PVN presympathetic neurons through PKC- and SNAP-25-mediated surface expression of NMDARs.}, keywords = {Blood Pressure, Rat, TRM54P}, pubstate = {published}, tppubtype = {article} } The hypothalamic paraventricular nucleus (PVN) is critically involved in elevated sympathetic output and the development of hypertension. However, changes in group I metabotropic glutamate receptors (mGluR1 and mGluR5) and their relevance to the hyperactivity of PVN presympathetic neurons in hypertension remain unclear. Here, we found that selectively blocking mGluR5 significantly reduced the basal firing activity of spinally projecting PVN neurons in spontaneously hypertensive rats (SHRs), but not in normotensive Wistar-Kyoto (WKY) rats. However, blocking mGluR1 had no effect on the firing activity of PVN neurons in either group. The mRNA and protein levels of mGluR5 in the PVN and rostral ventrolateral medulla were significantly higher in SHRs than in WKY rats. The group I mGluR selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) similarly increased the firing activity of PVN neurons in WKY rats and SHRs. In addition, blocking NMDA receptors (NMDARs) through bath application or intracellular dialysis not only decreased the basal firing in SHRs, but also eliminated DHPG-induced excitation of spinally projecting PVN neurons. DHPG significantly increased the amplitude of NMDAR currents without changing their decay kinetics. Interestingly, DHPG still increased the amplitude of NMDAR currents and caused reappearance of functional NMDAR channels after initially blocking NMDARs. In addition, protein kinase C (PKC) inhibition or intracellular dialysis with synaptosomal-associated protein of 25 kDa (SNAP-25)-blocking peptide abolished DHPG-induced increases in NMDAR currents of PVN neurons in SHRs. Our findings suggest that mGluR5 in the PVN is upregulated in hypertension and contributes to the hyperactivity of PVN presympathetic neurons through PKC- and SNAP-25-mediated surface expression of NMDARs.
|
|
Read, M I; Andreianova, A A; Harrison, J C; Goulton, C S; Sammut, I A; Kerr, D S Cardiac electrographic and morphological changes following status epilepticus: effect of clonidine Journal Article Seizure, 23 (1), pp. 55-61, 2014, ISBN: 1532-2688. Abstract | Links | BibTeX | Tags: ECG, EEG, Rat, TR50BB @article{RefWorks:doc:5c74bbb8e4b0b477ed402dec,
title = {Cardiac electrographic and morphological changes following status epilepticus: effect of clonidine}, author = {M I Read and A A Andreianova and J C Harrison and C S Goulton and I A Sammut and D S Kerr}, doi = {10.1016/j.seizure.2013.09.012}, isbn = {1532-2688}, year = {2014}, date = {2014-01-01}, journal = {Seizure}, volume = {23}, number = {1}, pages = {55-61}, abstract = {PURPOSE: Status epilepticus has been increasingly associated with cardiac injury in both clinical and animal studies. Our group has previously shown that excitotoxic seizure induction results in the formation of ischaemic myocardial infarcts and loss of cardiac haemodynamic function. We hypothesised that attenuation of cardiac sympathetic/parasympathetic balance with a central presynaptic alpha(2) agonist, clonidine, can reduce the development of interictal ECG and ventricular morphological changes resulting from kainic acid (KA; 10mg/kg) induced status epilepticus in a conscious rat model. METHODS: Using simultaneous ECG and electrocorticogram (ECoG) radiotelemetry, animals were randomised into saline controls, saline-pretreated KA and clonidine (100 mug/kg, b.i.d.)-pretreated KA groups. Baseline ECG, ECoG and behavioural score recordings were acquired in conscious animals for 2h post-KA administration. RESULTS: Bradycardia and low level seizure activity occurred immediately following KA administration. As seizure activity (ECoG spiking and high level seizure behavioural scoring) progressively increased, tachycardia developed. Both QTc prolongation and T wave amplitude were transiently but significantly increased. Clonidine treatment attenuated seizure activity, increased the latency to onset of seizure behaviour and reduced seizure-induced changes in heart rate, QTc interval, and T wave amplitude. Histological examination of the ventricular myocardium revealed hypercontraction band necrosis, inflammatory cell infiltration, and oedema at 48 h post-KA. In contrast, clonidine-treatment in seizure animals preserved tissue integrity and structure. CONCLUSION: These results demonstrate that KA-induced seizures are associated with altered ECG activity and cardiac structural pathology. We suggest that pharmacological modulation of sympathetic/parasympathetic activity in status epilepticus provides a promising therapeutic approach to reduce seizure-induced cardiomyopathy.}, keywords = {ECG, EEG, Rat, TR50BB}, pubstate = {published}, tppubtype = {article} } PURPOSE: Status epilepticus has been increasingly associated with cardiac injury in both clinical and animal studies. Our group has previously shown that excitotoxic seizure induction results in the formation of ischaemic myocardial infarcts and loss of cardiac haemodynamic function. We hypothesised that attenuation of cardiac sympathetic/parasympathetic balance with a central presynaptic alpha(2) agonist, clonidine, can reduce the development of interictal ECG and ventricular morphological changes resulting from kainic acid (KA; 10mg/kg) induced status epilepticus in a conscious rat model. METHODS: Using simultaneous ECG and electrocorticogram (ECoG) radiotelemetry, animals were randomised into saline controls, saline-pretreated KA and clonidine (100 mug/kg, b.i.d.)-pretreated KA groups. Baseline ECG, ECoG and behavioural score recordings were acquired in conscious animals for 2h post-KA administration. RESULTS: Bradycardia and low level seizure activity occurred immediately following KA administration. As seizure activity (ECoG spiking and high level seizure behavioural scoring) progressively increased, tachycardia developed. Both QTc prolongation and T wave amplitude were transiently but significantly increased. Clonidine treatment attenuated seizure activity, increased the latency to onset of seizure behaviour and reduced seizure-induced changes in heart rate, QTc interval, and T wave amplitude. Histological examination of the ventricular myocardium revealed hypercontraction band necrosis, inflammatory cell infiltration, and oedema at 48 h post-KA. In contrast, clonidine-treatment in seizure animals preserved tissue integrity and structure. CONCLUSION: These results demonstrate that KA-induced seizures are associated with altered ECG activity and cardiac structural pathology. We suggest that pharmacological modulation of sympathetic/parasympathetic activity in status epilepticus provides a promising therapeutic approach to reduce seizure-induced cardiomyopathy.
|
|
Han, J C; Goo, S; Barrett, C J; Mellor, K M; Taberner, A J; Loiselle, D S The afterload-dependent peak efficiency of the isolated working rat heart is unaffected by streptozotocin-induced diabetes Journal Article Cardiovascular diabetology, 13 , pp. 4, 2014, ISBN: 1475-2840. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM54P @article{RefWorks:doc:5c74a880e4b0b477ed402b6e,
title = {The afterload-dependent peak efficiency of the isolated working rat heart is unaffected by streptozotocin-induced diabetes}, author = {J C Han and S Goo and C J Barrett and K M Mellor and A J Taberner and D S Loiselle}, doi = {10.1186/1475-2840-13-4}, isbn = {1475-2840}, year = {2014}, date = {2014-01-01}, journal = {Cardiovascular diabetology}, volume = {13}, pages = {4}, abstract = {BACKGROUND: Diabetes is known to alter the energy metabolism of the heart. Thus, it may be expected to affect the efficiency of contraction (i.e., the ratio of mechanical work output to metabolic energy input). The literature on the subject is conflicting. The majority of studies have reported a reduction of myocardial efficiency of the diabetic heart, yet a number of studies have returned a null effect. We propose that these discrepant findings can be reconciled by examining the dependence of myocardial efficiency on afterload. METHODS: We performed experiments on streptozotocin (STZ)-induced diabetic rats (7-8 weeks post-induction), subjecting their (isolated) hearts to a wide range of afterloads (40 mmHg to maximal, where aortic flow approached zero). We measured work output and oxygen consumption, and their suitably scaled ratio (i.e., myocardial efficiency). RESULTS: We found that myocardial efficiency is a complex function of afterload: its value peaks in the mid-range and decreases on either side. Diabetes reduced the maximal afterload to which the hearts could pump (105 mmHg versus 150 mmHg). Thus, at high afterloads (for example, 90 mmHg), the efficiency of the STZ heart was lower than that of the healthy heart (10.4% versus 14.5%) due to its decreased work output. Diabetes also reduced the afterload at which peak efficiency occurred (optimal afterload: 63 mmHg versus 83 mmHg). Despite these negative effects, the peak value of myocardial efficiency (14.7%) was unaffected by diabetes. CONCLUSIONS: Diabetes reduces the ability of the heart to pump at high afterloads and, consequently, reduces the afterload at which peak efficiency occurs. However, the peak efficiency of the isolated working rat heart remains unaffected by STZ-induced diabetes.}, keywords = {Blood Pressure, Rat, TRM54P}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Diabetes is known to alter the energy metabolism of the heart. Thus, it may be expected to affect the efficiency of contraction (i.e., the ratio of mechanical work output to metabolic energy input). The literature on the subject is conflicting. The majority of studies have reported a reduction of myocardial efficiency of the diabetic heart, yet a number of studies have returned a null effect. We propose that these discrepant findings can be reconciled by examining the dependence of myocardial efficiency on afterload. METHODS: We performed experiments on streptozotocin (STZ)-induced diabetic rats (7-8 weeks post-induction), subjecting their (isolated) hearts to a wide range of afterloads (40 mmHg to maximal, where aortic flow approached zero). We measured work output and oxygen consumption, and their suitably scaled ratio (i.e., myocardial efficiency). RESULTS: We found that myocardial efficiency is a complex function of afterload: its value peaks in the mid-range and decreases on either side. Diabetes reduced the maximal afterload to which the hearts could pump (105 mmHg versus 150 mmHg). Thus, at high afterloads (for example, 90 mmHg), the efficiency of the STZ heart was lower than that of the healthy heart (10.4% versus 14.5%) due to its decreased work output. Diabetes also reduced the afterload at which peak efficiency occurred (optimal afterload: 63 mmHg versus 83 mmHg). Despite these negative effects, the peak value of myocardial efficiency (14.7%) was unaffected by diabetes. CONCLUSIONS: Diabetes reduces the ability of the heart to pump at high afterloads and, consequently, reduces the afterload at which peak efficiency occurs. However, the peak efficiency of the isolated working rat heart remains unaffected by STZ-induced diabetes.
|
2013 |
|
Stehlin, E; Malpas, S C; Budgett, D M; Barrett, C J; McCormick, D; Whalley, G; Fu, F; Beil, M; Rigel, D F; Guild, S J Chronic measurement of left ventricular pressure in freely moving rats Journal Article Journal of applied physiology (Bethesda, Md.: 1985), 115 (11), pp. 1672-1682, 2013, ISBN: 1522-1601. Abstract | Links | BibTeX | Tags: Blood Pressure, Left Ventricular Pressure, Rat, TRM54PP @article{RefWorks:doc:5c7498efe4b0947789160e08,
title = {Chronic measurement of left ventricular pressure in freely moving rats}, author = {E Stehlin and S C Malpas and D M Budgett and C J Barrett and D McCormick and G Whalley and F Fu and M Beil and D F Rigel and S J Guild}, doi = {10.1152/japplphysiol.00683.2013}, isbn = {1522-1601}, year = {2013}, date = {2013-12-01}, journal = {Journal of applied physiology (Bethesda, Md.: 1985)}, volume = {115}, number = {11}, pages = {1672-1682}, abstract = {Measurements of left ventricular pressure (LVP) in conscious freely moving animals are uncommon, yet could offer considerable opportunity for understanding cardiovascular disease progression and treatment. The aim of this study was to develop surgical methods and validate the measurements of a new high-fidelity, solid-state pressure-sensor telemetry device for chronically measuring LVP and dP/dt in rats. The pressure-sensor catheter tip (2-Fr) was inserted into the left ventricular chamber through the apex of the heart, and the telemeter body was implanted in the abdomen. Data were measured up to 85 days after implant. The average daytime dP/dt max was 9,444 +/- 363 mmHg/s, ranging from 7,870 to 10,558 mmHg/s (n = 7). A circadian variation in dP/dt max and heart rate (HR) was observed with an average increase during the night phase in dP/dt max of 918 +/- 84 mmHg/s, and in HR of 38 +/- 3 bpm. The beta-adrenergic-agonist isoproterenol, beta1-adrenergic agonist dobutamine, Ca(2+) channel blocker verapamil, and the calcium sensitizer levosimendan were administered throughout the implant period, inducing dose-dependent time course changes and absolute changes in dP/dt max of -6,000 to +13,000 mmHg/s. The surgical methods and new technologies demonstrated long-term stability, sensitivity to circadian variation, and the ability to measure large drug-induced changes, validating this new solution for chronic measurement of LVP in conscious rats.}, keywords = {Blood Pressure, Left Ventricular Pressure, Rat, TRM54PP}, pubstate = {published}, tppubtype = {article} } Measurements of left ventricular pressure (LVP) in conscious freely moving animals are uncommon, yet could offer considerable opportunity for understanding cardiovascular disease progression and treatment. The aim of this study was to develop surgical methods and validate the measurements of a new high-fidelity, solid-state pressure-sensor telemetry device for chronically measuring LVP and dP/dt in rats. The pressure-sensor catheter tip (2-Fr) was inserted into the left ventricular chamber through the apex of the heart, and the telemeter body was implanted in the abdomen. Data were measured up to 85 days after implant. The average daytime dP/dt max was 9,444 +/- 363 mmHg/s, ranging from 7,870 to 10,558 mmHg/s (n = 7). A circadian variation in dP/dt max and heart rate (HR) was observed with an average increase during the night phase in dP/dt max of 918 +/- 84 mmHg/s, and in HR of 38 +/- 3 bpm. The beta-adrenergic-agonist isoproterenol, beta1-adrenergic agonist dobutamine, Ca(2+) channel blocker verapamil, and the calcium sensitizer levosimendan were administered throughout the implant period, inducing dose-dependent time course changes and absolute changes in dP/dt max of -6,000 to +13,000 mmHg/s. The surgical methods and new technologies demonstrated long-term stability, sensitivity to circadian variation, and the ability to measure large drug-induced changes, validating this new solution for chronic measurement of LVP in conscious rats.
|
|
Stocker, S D; Muntzel, M S Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification Journal Article American journal of physiology.Heart and circulatory physiology, 305 (10), pp. 1407, 2013, ISBN: 1522-1539. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TRM56SP @article{RefWorks:doc:5c749d56e4b05c2b635402be,
title = {Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification}, author = {S D Stocker and M S Muntzel}, doi = {10.1152/ajpheart.00173.2013}, isbn = {1522-1539}, year = {2013}, date = {2013-11-01}, journal = {American journal of physiology.Heart and circulatory physiology}, volume = {305}, number = {10}, pages = {1407}, abstract = {The sympathetic nervous system plays a pivotal role in homeostasis through its direct innervation and functional impact on a variety of end organs. In rats, a number of methods are available to assess sympathetic nervous system function. Traditionally, direct recording of sympathetic nerve activity (SNA) has been restricted to acute, anesthetized preparations or conscious animals within a few days after electrode implantation. However, these approaches provide short-term data in studies designed to investigate changes in SNA during chronic disease states. Over the last several years, chronic SNA recording has been pioneered in rabbits and more recently in rats. The purpose of this article is to provide insights and a "how to" guide for chronic SNA recordings in rats based on experiences from two independent laboratories. We will present common methodologies used to chronically record SNA, characteristics and methods to distinguish sympathetic bursts versus electrical artifacts (and provide corresponding audio clips when available), and provide suggestions for analysis and presentation of data. In many instances, these same guidelines are applicable to acute SNA recordings. Using the surgical approaches described herein, both laboratories have been able to chronically record SNA in >50% of rats for a duration >3 wk. The ability to record SNA over the time course of several weeks will, undoubtedly, greatly impact the field of autonomic and cardiovascular physiology.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TRM56SP}, pubstate = {published}, tppubtype = {article} } The sympathetic nervous system plays a pivotal role in homeostasis through its direct innervation and functional impact on a variety of end organs. In rats, a number of methods are available to assess sympathetic nervous system function. Traditionally, direct recording of sympathetic nerve activity (SNA) has been restricted to acute, anesthetized preparations or conscious animals within a few days after electrode implantation. However, these approaches provide short-term data in studies designed to investigate changes in SNA during chronic disease states. Over the last several years, chronic SNA recording has been pioneered in rabbits and more recently in rats. The purpose of this article is to provide insights and a "how to" guide for chronic SNA recordings in rats based on experiences from two independent laboratories. We will present common methodologies used to chronically record SNA, characteristics and methods to distinguish sympathetic bursts versus electrical artifacts (and provide corresponding audio clips when available), and provide suggestions for analysis and presentation of data. In many instances, these same guidelines are applicable to acute SNA recordings. Using the surgical approaches described herein, both laboratories have been able to chronically record SNA in >50% of rats for a duration >3 wk. The ability to record SNA over the time course of several weeks will, undoubtedly, greatly impact the field of autonomic and cardiovascular physiology.
|
|
Casanova, J P; Contreras, M; Moya, E A; Torrealba, F; Iturriaga, R Effect of insular cortex inactivation on autonomic and behavioral responses to acute hypoxia in conscious rats Journal Article Behavioural brain research, 253 , pp. 60-67, 2013, ISBN: 1872-7549. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat @article{RefWorks:doc:5c749abce4b0947789160e72,
title = {Effect of insular cortex inactivation on autonomic and behavioral responses to acute hypoxia in conscious rats}, author = {J P Casanova and M Contreras and E A Moya and F Torrealba and R Iturriaga}, doi = {10.1016/j.bbr.2013.07.015}, isbn = {1872-7549}, year = {2013}, date = {2013-09-01}, journal = {Behavioural brain research}, volume = {253}, pages = {60-67}, abstract = {The present work was aimed to evaluate the contribution of interoception to the autonomic and behavioral responses to hypoxia. To address this issue, we studied whether the inactivation of the primary interoceptive posterior insular cortex (pIC) may disrupt the autonomic and behavioral effects of hypoxia in conscious rats. Rats were implanted with telemetric transmitters and microinjection cannulae placed bilaterally in the pIC. After one week, rats were injected with bupivacaine (26.5muM 1muL/side) and saline (1muL/side) into the pIC, and exposed to hypoxia ( approximately 6% O2) for 150s, and autonomic and behavioral responses were recorded. Hypoxia produces hypertension, tachycardia followed by bradycardia, and hypothermia. When O2 dropped to approximately 8%, rats showed escape behavior. Baseline cardiovascular variables and the pattern of hypoxia-induced autonomic and behavioral responses were not disrupted by pIC inactivation. However, pIC inactivation produced a modest but significant temperature decrease, higher bradycardic and hypertensive responses to hypoxia, and a minimal delay in escape onset. In addition, we measured the hypoxia-induced Fos activation in the nucleus tractus solitarius (NTS), the periaqueductal gray matter (PAG) and the pIC, which are key components of the interoceptive pathway. Hypoxia increased the number of Fos-positive neurons in the NTS and PAG, but not in the pIC. Present results suggest that pIC is not involved in the hypoxia-induced behavioral response, which seems to be processed in the NTS and PAG, but has a role in the efferent control of autonomic changes coping with hypoxia.}, keywords = {Blood Pressure, Rat}, pubstate = {published}, tppubtype = {article} } The present work was aimed to evaluate the contribution of interoception to the autonomic and behavioral responses to hypoxia. To address this issue, we studied whether the inactivation of the primary interoceptive posterior insular cortex (pIC) may disrupt the autonomic and behavioral effects of hypoxia in conscious rats. Rats were implanted with telemetric transmitters and microinjection cannulae placed bilaterally in the pIC. After one week, rats were injected with bupivacaine (26.5muM 1muL/side) and saline (1muL/side) into the pIC, and exposed to hypoxia ( approximately 6% O2) for 150s, and autonomic and behavioral responses were recorded. Hypoxia produces hypertension, tachycardia followed by bradycardia, and hypothermia. When O2 dropped to approximately 8%, rats showed escape behavior. Baseline cardiovascular variables and the pattern of hypoxia-induced autonomic and behavioral responses were not disrupted by pIC inactivation. However, pIC inactivation produced a modest but significant temperature decrease, higher bradycardic and hypertensive responses to hypoxia, and a minimal delay in escape onset. In addition, we measured the hypoxia-induced Fos activation in the nucleus tractus solitarius (NTS), the periaqueductal gray matter (PAG) and the pIC, which are key components of the interoceptive pathway. Hypoxia increased the number of Fos-positive neurons in the NTS and PAG, but not in the pIC. Present results suggest that pIC is not involved in the hypoxia-induced behavioral response, which seems to be processed in the NTS and PAG, but has a role in the efferent control of autonomic changes coping with hypoxia.
|
|
Zena, L A; Gargaglioni, L H; Bicego, K C Role of brain nitric oxide in the cardiovascular control of bullfrogs Journal Article Comparative biochemistry and physiology.Part A, Molecular & integrative physiology, 165 (2), pp. 263-271, 2013, ISBN: 1531-4332. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TR43P @article{RefWorks:doc:5c749d6ce4b073ca706af85b,
title = {Role of brain nitric oxide in the cardiovascular control of bullfrogs}, author = {L A Zena and L H Gargaglioni and K C Bicego}, doi = {10.1016/j.cbpa.2013.03.020}, isbn = {1531-4332}, year = {2013}, date = {2013-06-01}, journal = {Comparative biochemistry and physiology.Part A, Molecular & integrative physiology}, volume = {165}, number = {2}, pages = {263-271}, abstract = {The goal of the present study was to determine if nitric oxide (NO) acting on the brain of bullfrog (Lithobates catesbeianus) is involved in arterial pressure and heart rate (HR) control by influencing sympathetic activity. We investigated the effect of intracerebroventricular injections of L-NMMA (a nonselective NO synthase inhibitor) on mean arterial blood pressure (MAP), HR and cutaneous vascular conductance (CVC) of pelvic skin after intravenous injection of alpha or beta adrenergic blockers, prazosin or sotalol, respectively. Arterial pressure was directly measured by a telemetry sensor inserted in the aortic arch of animals. L-NMMA increased MAP, but did not change HR. This hypertensive response was inhibited by the pre-treatment with prazosin, but accentuated by sotalol. The effect of L-NMMA on MAP was also inhibited by i.v. injections of the ganglionic blocker, hexamethonium. Thus, NO acting on the brain of bullfrog seems to present a hypotensive effect influencing the sympathetic activity dependent on alpha and beta adrenergic receptors in the periphery.}, keywords = {Blood Pressure, Rat, TR43P}, pubstate = {published}, tppubtype = {article} } The goal of the present study was to determine if nitric oxide (NO) acting on the brain of bullfrog (Lithobates catesbeianus) is involved in arterial pressure and heart rate (HR) control by influencing sympathetic activity. We investigated the effect of intracerebroventricular injections of L-NMMA (a nonselective NO synthase inhibitor) on mean arterial blood pressure (MAP), HR and cutaneous vascular conductance (CVC) of pelvic skin after intravenous injection of alpha or beta adrenergic blockers, prazosin or sotalol, respectively. Arterial pressure was directly measured by a telemetry sensor inserted in the aortic arch of animals. L-NMMA increased MAP, but did not change HR. This hypertensive response was inhibited by the pre-treatment with prazosin, but accentuated by sotalol. The effect of L-NMMA on MAP was also inhibited by i.v. injections of the ganglionic blocker, hexamethonium. Thus, NO acting on the brain of bullfrog seems to present a hypotensive effect influencing the sympathetic activity dependent on alpha and beta adrenergic receptors in the periphery.
|
|
Koeners, M P; Ow, C P; Russell, D M; Abdelkader, A; Eppel, G A; Ludbrook, J; Malpas, S C; Evans, R G Telemetry-based oxygen sensor for continuous monitoring of kidney oxygenation in conscious rats Journal Article American journal of physiology.Renal physiology, 304 (12), pp. 1471, 2013, ISBN: 1522-1466. Abstract | Links | BibTeX | Tags: Oxygen, Rat, TR57Y @article{RefWorks:doc:5c749c41e4b0947789160ec4,
title = {Telemetry-based oxygen sensor for continuous monitoring of kidney oxygenation in conscious rats}, author = {M P Koeners and C P Ow and D M Russell and A Abdelkader and G A Eppel and J Ludbrook and S C Malpas and R G Evans}, doi = {10.1152/ajprenal.00662.2012}, isbn = {1522-1466}, year = {2013}, date = {2013-06-01}, journal = {American journal of physiology.Renal physiology}, volume = {304}, number = {12}, pages = {1471}, abstract = {The precise roles of hypoxia in the initiation and progression of kidney disease remain unresolved. A major technical limitation has been the absence of methods allowing long-term measurement of kidney tissue oxygen tension (Po(2)) in unrestrained animals. We developed a telemetric method for the measurement of kidney tissue Po(2) in unrestrained rats, using carbon paste electrodes (CPEs). After acute implantation in anesthetized rats, tissue Po(2) measured by CPE-telemetry in the inner cortex and medulla was in close agreement with that provided by the "gold standard" Clark electrode. The CPE-telemetry system could detect small changes in renal tissue Po(2) evoked by mild hypoxemia. In unanesthetized rats, CPE-telemetry provided stable measurements of medullary tissue Po(2) over days 5-19 after implantation. It also provided reproducible responses to systemic hypoxia and hyperoxia over this time period. There was little evidence of fibrosis or scarring after 3 wk of electrode implantation. However, because medullary Po(2) measured by CPE-telemetry was greater than that documented from previous studies in anesthetized animals, this method is presently best suited for monitoring relative changes rather than absolute values. Nevertheless, this new technology provides, for the first time, the opportunity to examine the temporal relationships between tissue hypoxia and the progression of renal disease.}, keywords = {Oxygen, Rat, TR57Y}, pubstate = {published}, tppubtype = {article} } The precise roles of hypoxia in the initiation and progression of kidney disease remain unresolved. A major technical limitation has been the absence of methods allowing long-term measurement of kidney tissue oxygen tension (Po(2)) in unrestrained animals. We developed a telemetric method for the measurement of kidney tissue Po(2) in unrestrained rats, using carbon paste electrodes (CPEs). After acute implantation in anesthetized rats, tissue Po(2) measured by CPE-telemetry in the inner cortex and medulla was in close agreement with that provided by the "gold standard" Clark electrode. The CPE-telemetry system could detect small changes in renal tissue Po(2) evoked by mild hypoxemia. In unanesthetized rats, CPE-telemetry provided stable measurements of medullary tissue Po(2) over days 5-19 after implantation. It also provided reproducible responses to systemic hypoxia and hyperoxia over this time period. There was little evidence of fibrosis or scarring after 3 wk of electrode implantation. However, because medullary Po(2) measured by CPE-telemetry was greater than that documented from previous studies in anesthetized animals, this method is presently best suited for monitoring relative changes rather than absolute values. Nevertheless, this new technology provides, for the first time, the opportunity to examine the temporal relationships between tissue hypoxia and the progression of renal disease.
|
|
Lau, S Y; Barrett, C J; Guild, S J; Chamley, L W Necrotic trophoblast debris increases blood pressure during pregnancy Journal Article Journal of reproductive immunology, 97 (2), pp. 175-182, 2013, ISBN: 1872-7603. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM53P @article{RefWorks:doc:5c749c62e4b02df9431d7cdd,
title = {Necrotic trophoblast debris increases blood pressure during pregnancy}, author = {S Y Lau and C J Barrett and S J Guild and L W Chamley}, doi = {10.1016/j.jri.2012.12.005}, isbn = {1872-7603}, year = {2013}, date = {2013-04-01}, journal = {Journal of reproductive immunology}, volume = {97}, number = {2}, pages = {175-182}, abstract = {Preeclampsia is a major disease of human pregnancy characterised by hypertension and proteinuria. These signs are preceded by systemic maternal endothelial dysfunction. Hypertension in preeclampsia appears to be triggered by a placental factor, which leads to endothelial activation/dysfunction. One potential placental trigger for preeclampsia is necrotic trophoblast cell debris shed from the placenta into maternal blood. The larger trophoblast debris is trapped in the maternal pulmonary vessels and is hypothesised to be cleared by endothelial cells. Phagocytosis of necrotic but not apoptotic trophoblast debris by endothelial cells leads to their activation in vitro. We hypothesised that intravenous injection of necrotic trophoblast debris would induce hypertension in pregnant rats. Virgin female Wistar rats were surgically implanted with telemetry devices to monitor arterial blood pressure and chronic intravenous catheters to allow delivery of necrotic trophoblast debris. After recovery, the rats were mated and, from day 6 of gestation until parturition, they were given five consecutive daily injections per week of 5x10(6) necrotic Jeg-3 cells per kilo bodyweight. Control rats received vehicle injections. The normalised mean arterial blood pressure of rats receiving injections of necrotic trophoblast debris was higher than control rats during the third week of gestation, while mean arterial blood pressure decreased less from the pre-pregnancy baseline compared to control rats. These results suggest that necrotic trophoblast debris has a hypertensive effect which manifests in late gestation in Wistar rats and supports the theory that necrotic trophoblast debris may trigger the symptoms of preeclampsia.}, keywords = {Blood Pressure, Rat, TRM53P}, pubstate = {published}, tppubtype = {article} } Preeclampsia is a major disease of human pregnancy characterised by hypertension and proteinuria. These signs are preceded by systemic maternal endothelial dysfunction. Hypertension in preeclampsia appears to be triggered by a placental factor, which leads to endothelial activation/dysfunction. One potential placental trigger for preeclampsia is necrotic trophoblast cell debris shed from the placenta into maternal blood. The larger trophoblast debris is trapped in the maternal pulmonary vessels and is hypothesised to be cleared by endothelial cells. Phagocytosis of necrotic but not apoptotic trophoblast debris by endothelial cells leads to their activation in vitro. We hypothesised that intravenous injection of necrotic trophoblast debris would induce hypertension in pregnant rats. Virgin female Wistar rats were surgically implanted with telemetry devices to monitor arterial blood pressure and chronic intravenous catheters to allow delivery of necrotic trophoblast debris. After recovery, the rats were mated and, from day 6 of gestation until parturition, they were given five consecutive daily injections per week of 5x10(6) necrotic Jeg-3 cells per kilo bodyweight. Control rats received vehicle injections. The normalised mean arterial blood pressure of rats receiving injections of necrotic trophoblast debris was higher than control rats during the third week of gestation, while mean arterial blood pressure decreased less from the pre-pregnancy baseline compared to control rats. These results suggest that necrotic trophoblast debris has a hypertensive effect which manifests in late gestation in Wistar rats and supports the theory that necrotic trophoblast debris may trigger the symptoms of preeclampsia.
|
|
McBryde, F D; Abdala, A P; Hendy, E B; Pijacka, W; Marvar, P; Moraes, D J; Sobotka, P A; Paton, J F The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension Journal Article Nature communications, 4 , pp. 2395, 2013, ISBN: 2041-1723. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c749cb0e4b01022d49de625,
title = {The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension}, author = {F D McBryde and A P Abdala and E B Hendy and W Pijacka and P Marvar and D J Moraes and P A Sobotka and J F Paton}, doi = {10.1038/ncomms3395}, isbn = {2041-1723}, year = {2013}, date = {2013-01-01}, journal = {Nature communications}, volume = {4}, pages = {2395}, abstract = {In the spontaneously hypertensive (SH) rat, hyperoxic inactivation of the carotid body (CB) produces a rapid and pronounced fall in both arterial pressure and renal sympathetic nerve activity (RSA). Here we show that CB de-afferentation through carotid sinus nerve denervation (CSD) reduces the overactive sympathetic activity in SH rats, providing an effective antihypertensive treatment. We demonstrate that CSD lowers RSA chronically and that this is accompanied by a depressor response in SH but not normotensive rats. The drop in blood pressure is not dependent on renal nerve integrity but mechanistically accompanied by a resetting of the RSA-baroreflex function curve, sensitization of the cardiac baroreflex, changes in renal excretory function and reduced T-lymphocyte infiltration. We further show that combined with renal denervation, CSD remains effective, producing a summative response indicative of an independent mechanism. Our findings indicate that CB de-afferentation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } In the spontaneously hypertensive (SH) rat, hyperoxic inactivation of the carotid body (CB) produces a rapid and pronounced fall in both arterial pressure and renal sympathetic nerve activity (RSA). Here we show that CB de-afferentation through carotid sinus nerve denervation (CSD) reduces the overactive sympathetic activity in SH rats, providing an effective antihypertensive treatment. We demonstrate that CSD lowers RSA chronically and that this is accompanied by a depressor response in SH but not normotensive rats. The drop in blood pressure is not dependent on renal nerve integrity but mechanistically accompanied by a resetting of the RSA-baroreflex function curve, sensitization of the cardiac baroreflex, changes in renal excretory function and reduced T-lymphocyte infiltration. We further show that combined with renal denervation, CSD remains effective, producing a summative response indicative of an independent mechanism. Our findings indicate that CB de-afferentation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension.
|
|
Marina, N; Tang, F; Figueiredo, M; Mastitskaya, S; Kasimov, V; Mohamed-Ali, V; Roloff, E; Teschemacher, A G; Gourine, A V; Kasparov, S Basic research in cardiology, 108 (1), pp. x. Epub 2012 Nov 28, 2013, ISBN: 1435-1803. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c749c83e4b01022d49de622,
title = {Purinergic signalling in the rostral ventro-lateral medulla controls sympathetic drive and contributes to the progression of heart failure following myocardial infarction in rats}, author = {N Marina and F Tang and M Figueiredo and S Mastitskaya and V Kasimov and V Mohamed-Ali and E Roloff and A G Teschemacher and A V Gourine and S Kasparov}, doi = {10.1007/s00395-012-0317-x}, isbn = {1435-1803}, year = {2013}, date = {2013-01-01}, journal = {Basic research in cardiology}, volume = {108}, number = {1}, pages = {x. Epub 2012 Nov 28}, abstract = {Heart failure may lead to hypoperfusion and hypooxygenation of tissues and this is often exacerbated by central and obstructive sleep apnoeas associated with recurrent episodes of systemic hypoxia which triggers release of ATP within the CNS circuits controlling sympathetic outflow. Using in vitro and in vivo models we tested two hypotheses: (1) activated brainstem astroglia release ATP and via release of ATP activate sympathoexcitatory neurones of the rostral ventrolateral medulla (RVLM); and (2) ATP actions in the RVLM contribute to sympathoexcitation, progression of left ventricular (LV) remodelling and development heart failure secondary to myocardial infarction. In vitro, optogenetic activation of RVLM astrocytes transduced to express light-sensitive channelrhodopsin-2 activated sympathoexcitatory RVLM neurones in ATP-dependent manner. In anaesthetised rats in vivo, similar optogenetic activation of RVLM astrocytes increased sympathetic renal nerve activity, arterial blood pressure and heart rate. To interfere with ATP-mediated signalling by promoting its extracellular breakdown, we developed a lentiviral vector to express an ectonucleotidase--transmembrane prostatic acid phosphatase (TMPAP) on the cellular membranes. In rats with myocardial infarction-induced heart failure, expression of TMPAP bilaterally in the RVLM led to lower plasma noradrenaline concentration, maintained left ventricular end diastolic pressure, attenuated decline in dP/dT (max) and shifted the LV pressure-volume relationship curve to the left. These results show that activated RVLM astrocytes are capable of increasing sympathetic activity via release of ATP while facilitated breakdown of ATP in the RVLM attenuates the progression of LV remodelling and heart failure secondary to myocardial infarction.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } Heart failure may lead to hypoperfusion and hypooxygenation of tissues and this is often exacerbated by central and obstructive sleep apnoeas associated with recurrent episodes of systemic hypoxia which triggers release of ATP within the CNS circuits controlling sympathetic outflow. Using in vitro and in vivo models we tested two hypotheses: (1) activated brainstem astroglia release ATP and via release of ATP activate sympathoexcitatory neurones of the rostral ventrolateral medulla (RVLM); and (2) ATP actions in the RVLM contribute to sympathoexcitation, progression of left ventricular (LV) remodelling and development heart failure secondary to myocardial infarction. In vitro, optogenetic activation of RVLM astrocytes transduced to express light-sensitive channelrhodopsin-2 activated sympathoexcitatory RVLM neurones in ATP-dependent manner. In anaesthetised rats in vivo, similar optogenetic activation of RVLM astrocytes increased sympathetic renal nerve activity, arterial blood pressure and heart rate. To interfere with ATP-mediated signalling by promoting its extracellular breakdown, we developed a lentiviral vector to express an ectonucleotidase--transmembrane prostatic acid phosphatase (TMPAP) on the cellular membranes. In rats with myocardial infarction-induced heart failure, expression of TMPAP bilaterally in the RVLM led to lower plasma noradrenaline concentration, maintained left ventricular end diastolic pressure, attenuated decline in dP/dT (max) and shifted the LV pressure-volume relationship curve to the left. These results show that activated RVLM astrocytes are capable of increasing sympathetic activity via release of ATP while facilitated breakdown of ATP in the RVLM attenuates the progression of LV remodelling and heart failure secondary to myocardial infarction.
|
2012 |
|
Muntzel, M S; Al-Naimi, O A; Barclay, A; Ajasin, D Cafeteria diet increases fat mass and chronically elevates lumbar sympathetic nerve activity in rats Journal Article Hypertension (Dallas, Tex.: 1979), 60 (6), pp. 1498-1502, 2012, ISBN: 1524-4563. Abstract | Links | BibTeX | Tags: Rat, Sympathetic Nerve Activity @article{RefWorks:doc:5c7499ebe4b07cf352f5d5ed,
title = {Cafeteria diet increases fat mass and chronically elevates lumbar sympathetic nerve activity in rats}, author = {M S Muntzel and O A Al-Naimi and A Barclay and D Ajasin}, doi = {10.1161/HYPERTENSIONAHA.112.194886}, isbn = {1524-4563}, year = {2012}, date = {2012-12-01}, journal = {Hypertension (Dallas, Tex.: 1979)}, volume = {60}, number = {6}, pages = {1498-1502}, abstract = {Obesity causes sympathetic activation that promotes atherosclerosis, end-organ damage, and hypertension. Because high-fat induced weight gain in rats elevates plasma leptin at 1 to 3 days after the onset of calorie-dense diets, we hypothesized that diet-induced overfeeding will increase sympathetic activity within 1 week after the onset of the regimen. To test this, we continuously measured sympathetic activity and blood pressure before and during the onset of diet-induced obesity using a high-calorie, cafeteria-style diet. Female Wistar rats, in which radiotelemeters had been implanted for continuous monitoring of lumbar sympathetic activity, mean arterial pressure, and heart rate, were randomly assigned to groups that received regular chow (control) or a cafeteria diet for a period of 15 days. This short-term, cafeteria-feeding regimen caused modest but nonsignificant increases in body weight (P=0.07) and a doubling of brown and white adipose tissue (P<0.01). The increases in fat mass were accompanied by elevations in plasma leptin (P<0.001) but no change in glucose. Overall heart rates and blood pressure were higher in cafeteria rats compared with controls (P<0.05). Cafeteria diet-induced weight gain caused increases in lumbar sympathetic nerve activity that became significant by the 12th day of the diet (P<0.001). These data show, for the first time, that the high-fat, cafeteria-style diet stimulates sustained increases in lumbar sympathetic neural drive in rats.}, keywords = {Rat, Sympathetic Nerve Activity}, pubstate = {published}, tppubtype = {article} } Obesity causes sympathetic activation that promotes atherosclerosis, end-organ damage, and hypertension. Because high-fat induced weight gain in rats elevates plasma leptin at 1 to 3 days after the onset of calorie-dense diets, we hypothesized that diet-induced overfeeding will increase sympathetic activity within 1 week after the onset of the regimen. To test this, we continuously measured sympathetic activity and blood pressure before and during the onset of diet-induced obesity using a high-calorie, cafeteria-style diet. Female Wistar rats, in which radiotelemeters had been implanted for continuous monitoring of lumbar sympathetic activity, mean arterial pressure, and heart rate, were randomly assigned to groups that received regular chow (control) or a cafeteria diet for a period of 15 days. This short-term, cafeteria-feeding regimen caused modest but nonsignificant increases in body weight (P=0.07) and a doubling of brown and white adipose tissue (P<0.01). The increases in fat mass were accompanied by elevations in plasma leptin (P<0.001) but no change in glucose. Overall heart rates and blood pressure were higher in cafeteria rats compared with controls (P<0.05). Cafeteria diet-induced weight gain caused increases in lumbar sympathetic nerve activity that became significant by the 12th day of the diet (P<0.001). These data show, for the first time, that the high-fat, cafeteria-style diet stimulates sustained increases in lumbar sympathetic neural drive in rats.
|
|
Pinkham, M I; Guild, S J; Malpas, S C; Barrett, C J Effects of sex and ovarian hormones on the initial renal sympathetic nerve activity response to myocardial infarction Journal Article Experimental physiology, 97 (9), pp. 1040-1053, 2012, ISBN: 1469-445X. Abstract | Links | BibTeX | Tags: Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c749a12e4b01022d49de5bc,
title = {Effects of sex and ovarian hormones on the initial renal sympathetic nerve activity response to myocardial infarction}, author = {M I Pinkham and S J Guild and S C Malpas and C J Barrett}, doi = {10.1113/expphysiol.2012.065615}, isbn = {1469-445X}, year = {2012}, date = {2012-09-01}, journal = {Experimental physiology}, volume = {97}, number = {9}, pages = {1040-1053}, abstract = {The physiological mechanisms contributing to sex differences following myocardial infarction (MI) are poorly understood. Given the strong relationship between sympathetic nerve activity (SNA) and outcome, we hypothesized there may be a sex difference in SNA responses to MI. In anaesthetized, open-chest male, female and ovariectomized (OVX) female Wistar rats, mean arterial pressure, heart rate and renal SNA were recorded in response to ligation of the left coronary artery. In males, renal SNA increased by 30 +/- 6% in the first minute of coronary occlusion (P < 0.05) and remained elevated at 18 +/- 7% above baseline (P < 0.05) at 2 h following MI. In response to MI, ovary-intact females displayed no change in renal SNA, whereas OVX females displayed a significant increase, similar to that seen in the males (increases of 43 +/- 11% at 1 min and 21 +/- 7% at 2 h post-MI, P < 0.05 versus intact females). Arterial baroreflex control of renal SNA had a smaller range in females (ovary intact and OVX) than males; no changes in arterial baroreflex responses were observed 1 h post-MI in males or females. Denervating the arterial baroreceptors abolished the renal SNA response to MI in the males, whereas in ovary-intact females and OVX females the response was unaltered. These findings suggest that ovarian hormones are able to blunt the initial sympathetic activation post-MI in females and that the importance of the arterial baroreflex in mediating initial sympathetic activation post-MI is different between the sexes.}, keywords = {Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } The physiological mechanisms contributing to sex differences following myocardial infarction (MI) are poorly understood. Given the strong relationship between sympathetic nerve activity (SNA) and outcome, we hypothesized there may be a sex difference in SNA responses to MI. In anaesthetized, open-chest male, female and ovariectomized (OVX) female Wistar rats, mean arterial pressure, heart rate and renal SNA were recorded in response to ligation of the left coronary artery. In males, renal SNA increased by 30 +/- 6% in the first minute of coronary occlusion (P < 0.05) and remained elevated at 18 +/- 7% above baseline (P < 0.05) at 2 h following MI. In response to MI, ovary-intact females displayed no change in renal SNA, whereas OVX females displayed a significant increase, similar to that seen in the males (increases of 43 +/- 11% at 1 min and 21 +/- 7% at 2 h post-MI, P < 0.05 versus intact females). Arterial baroreflex control of renal SNA had a smaller range in females (ovary intact and OVX) than males; no changes in arterial baroreflex responses were observed 1 h post-MI in males or females. Denervating the arterial baroreceptors abolished the renal SNA response to MI in the males, whereas in ovary-intact females and OVX females the response was unaltered. These findings suggest that ovarian hormones are able to blunt the initial sympathetic activation post-MI in females and that the importance of the arterial baroreflex in mediating initial sympathetic activation post-MI is different between the sexes.
|
|
Ye, Z Y; Li, D P; Byun, H S; Li, L; Pan, H L NKCC1 upregulation disrupts chloride homeostasis in the hypothalamus and increases neuronal activity-sympathetic drive in hypertension Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (25), pp. 8560-8568, 2012, ISBN: 1529-2401. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat @article{RefWorks:doc:5c749a5be4b02df9431d7cbe,
title = {NKCC1 upregulation disrupts chloride homeostasis in the hypothalamus and increases neuronal activity-sympathetic drive in hypertension}, author = {Z Y Ye and D P Li and H S Byun and L Li and H L Pan}, doi = {10.1523/JNEUROSCI.1346-12.2012}, isbn = {1529-2401}, year = {2012}, date = {2012-06-01}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {32}, number = {25}, pages = {8560-8568}, abstract = {Hypertension is a major risk factor for coronary artery disease, stroke, and kidney failure. However, the etiology of hypertension in most patients is poorly understood. Increased sympathetic drive emanating from the hypothalamic paraventricular nucleus (PVN) plays a major role in the development of hypertension. Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) in the brain is critically involved in maintaining chloride homeostasis and in neuronal responses mediated by GABA(A) receptors. Here we present novel evidence that the GABA reversal potential (E(GABA)) of PVN presympathetic neurons undergoes a depolarizing shift that diminishes GABA inhibition in spontaneously hypertensive rats (SHRs). Inhibition of NKCC1, but not KCC2, normalizes E(GABA) and restores GABA inhibition of PVN neurons in SHRs. The mRNA and protein levels of NKCC1, but not KCC2, in the PVN are significantly increased in SHRs, and the NKCC1 proteins on the plasma membrane are highly glycosylated. Inhibiting NKCC1 N-glycosylation restores E(GABA) and GABAergic inhibition of PVN presympathetic neurons in SHRs. Furthermore, NKCC1 inhibition significantly reduces the sympathetic vasomotor tone and augments the sympathoinhibitory responses to GABA(A) receptor activation in the PVN in SHRs. These findings suggest that increased NKCC1 activity and glycosylation disrupt chloride homeostasis and impair synaptic inhibition in the PVN to augment the sympathetic drive in hypertension. This information greatly improves our understanding of the pathogenesis of hypertension and helps to design better treatment strategies for neurogenic hypertension.}, keywords = {Blood Pressure, Rat}, pubstate = {published}, tppubtype = {article} } Hypertension is a major risk factor for coronary artery disease, stroke, and kidney failure. However, the etiology of hypertension in most patients is poorly understood. Increased sympathetic drive emanating from the hypothalamic paraventricular nucleus (PVN) plays a major role in the development of hypertension. Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) in the brain is critically involved in maintaining chloride homeostasis and in neuronal responses mediated by GABA(A) receptors. Here we present novel evidence that the GABA reversal potential (E(GABA)) of PVN presympathetic neurons undergoes a depolarizing shift that diminishes GABA inhibition in spontaneously hypertensive rats (SHRs). Inhibition of NKCC1, but not KCC2, normalizes E(GABA) and restores GABA inhibition of PVN neurons in SHRs. The mRNA and protein levels of NKCC1, but not KCC2, in the PVN are significantly increased in SHRs, and the NKCC1 proteins on the plasma membrane are highly glycosylated. Inhibiting NKCC1 N-glycosylation restores E(GABA) and GABAergic inhibition of PVN presympathetic neurons in SHRs. Furthermore, NKCC1 inhibition significantly reduces the sympathetic vasomotor tone and augments the sympathoinhibitory responses to GABA(A) receptor activation in the PVN in SHRs. These findings suggest that increased NKCC1 activity and glycosylation disrupt chloride homeostasis and impair synaptic inhibition in the PVN to augment the sympathetic drive in hypertension. This information greatly improves our understanding of the pathogenesis of hypertension and helps to design better treatment strategies for neurogenic hypertension.
|
|
Russell, D M; Garry, E M; Taberner, A J; Barrett, C J; Paton, J F; Budgett, D M; Malpas, S C A fully implantable telemetry system for the chronic monitoring of brain tissue oxygen in freely moving rats Journal Article Journal of neuroscience methods, 204 (2), pp. 242-248, 2012, ISBN: 1872-678X. Abstract | Links | BibTeX | Tags: Oxygen, Rat, TR57Y @article{RefWorks:doc:5c749a39e4b0947789160e50,
title = {A fully implantable telemetry system for the chronic monitoring of brain tissue oxygen in freely moving rats}, author = {D M Russell and E M Garry and A J Taberner and C J Barrett and J F Paton and D M Budgett and S C Malpas}, doi = {10.1016/j.jneumeth.2011.11.019}, isbn = {1872-678X}, year = {2012}, date = {2012-03-01}, journal = {Journal of neuroscience methods}, volume = {204}, number = {2}, pages = {242-248}, abstract = {The ability to monitor tissue oxygen concentration in a specific region of the brain in a freely moving animal could provide a new paradigm in neuroscience research. We have developed a fully implantable telemetry system for the continuous and chronic recording of brain tissue oxygen (PO(2,BR)) in conscious animals. A telemetry system with a sampling rate of 2kHz was combined with a miniaturized potentiostat to amperiometrically detect oxygen concentration with carbon paste electrodes. Wireless power was employed to recharge the telemeter battery transcutaneously for potential lifetime monitoring. Rats were implanted with the telemeter in the peritoneal cavity and electrodes stereotaxically implanted into the brain (striatum or medulla oblongata). While the animals were living in their home cages the sensitivity to changes in oxygen was validated by repeatedly altering the inspired oxygen (10%, 100%, respectively) or a pharmacological stimulus (carbonic anhydrase inhibitor: acetazolamide 50mg/kg IP). Basal level of PO(2,BR) was monitored for 3weeks and showed good overall stability and good correlation to movement such as grooming. During hypoxia, PO(2,BR) decreased significantly by -51%+/-2% from baseline, whereas it increased by 34%+/-3% during hyperoxia. Following the systemic administration of acetazolamide, PO(2,BR) increased by 38%+/-4%. We propose this new technology provides a robust method to measure changes in oxygen concentration in specific areas of the brain, in conscious freely moving rats. The ability to track long term changes with disease progression or drug treatment may be enabled.}, keywords = {Oxygen, Rat, TR57Y}, pubstate = {published}, tppubtype = {article} } The ability to monitor tissue oxygen concentration in a specific region of the brain in a freely moving animal could provide a new paradigm in neuroscience research. We have developed a fully implantable telemetry system for the continuous and chronic recording of brain tissue oxygen (PO(2,BR)) in conscious animals. A telemetry system with a sampling rate of 2kHz was combined with a miniaturized potentiostat to amperiometrically detect oxygen concentration with carbon paste electrodes. Wireless power was employed to recharge the telemeter battery transcutaneously for potential lifetime monitoring. Rats were implanted with the telemeter in the peritoneal cavity and electrodes stereotaxically implanted into the brain (striatum or medulla oblongata). While the animals were living in their home cages the sensitivity to changes in oxygen was validated by repeatedly altering the inspired oxygen (10%, 100%, respectively) or a pharmacological stimulus (carbonic anhydrase inhibitor: acetazolamide 50mg/kg IP). Basal level of PO(2,BR) was monitored for 3weeks and showed good overall stability and good correlation to movement such as grooming. During hypoxia, PO(2,BR) decreased significantly by -51%+/-2% from baseline, whereas it increased by 34%+/-3% during hyperoxia. Following the systemic administration of acetazolamide, PO(2,BR) increased by 38%+/-4%. We propose this new technology provides a robust method to measure changes in oxygen concentration in specific areas of the brain, in conscious freely moving rats. The ability to track long term changes with disease progression or drug treatment may be enabled.
|
|
Li, D P; Byan, H S; Pan, H L Switch to glutamate receptor 2-lacking AMPA receptors increases neuronal excitability in hypothalamus and sympathetic drive in hypertension Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (1), pp. 372-380, 2012, ISBN: 1529-2401. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, TRM54P @article{RefWorks:doc:5c7499c1e4b00e57e1f361e2,
title = {Switch to glutamate receptor 2-lacking AMPA receptors increases neuronal excitability in hypothalamus and sympathetic drive in hypertension}, author = {D P Li and H S Byan and H L Pan}, doi = {10.1523/JNEUROSCI.3222-11.2012}, isbn = {1529-2401}, year = {2012}, date = {2012-01-01}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {32}, number = {1}, pages = {372-380}, abstract = {Glutamatergic synaptic input in the hypothalamic paraventricular nucleus (PVN) plays a critical role in regulating sympathetic outflow in hypertension. GluR2-lacking AMPA receptors (AMPARs) are permeable to Ca(2+), and their currents show unique inward rectification. However, little is known about changes in the AMPAR composition and its functional significance in hypertension. In this study, we found that AMPAR-mediated EPSCs (AMPAR-EPSCs) of retrogradely labeled spinally projecting PVN neurons exhibited a linear current-voltage relationship in Wistar-Kyoto (WKY) rats. However, AMPAR-EPSCs of labeled PVN neurons in spontaneously hypertensive rats (SHR) displayed inward rectification at positive holding potentials, which were not altered by lowering blood pressure with celiac ganglionectomy. Blocking GluR2-lacking AMPARs with 1-naphthyl acetyl spermine (NAS) caused a greater reduction in the AMPAR-EPSC amplitude and firing activity of PVN neurons in SHR than in WKY rats. Furthermore, blocking NMDA receptors and inhibition of calpain or calcineurin abolished inward rectification of AMPAR-EPSCs of PVN neurons in SHR. The GluR2 protein level was significantly less in the plasma membrane but greater in the cytosolic vesicle fraction in SHR than in WKY rats. In addition, microinjection of NAS into the PVN decreased blood pressure and lumbar sympathetic nerve activity in SHR but not in WKY rats. Our study reveals that increased GluR2-lacking AMPAR activity of PVN neurons results from GluR2 internalization through NMDA receptor-calpain-calcineurin signaling in hypertension. This phenotype switch in synaptic AMPARs contributes to increased excitability of PVN presympathetic neurons and sympathetic vasomotor tone in hypertension.}, keywords = {Blood Pressure, Rat, TRM54P}, pubstate = {published}, tppubtype = {article} } Glutamatergic synaptic input in the hypothalamic paraventricular nucleus (PVN) plays a critical role in regulating sympathetic outflow in hypertension. GluR2-lacking AMPA receptors (AMPARs) are permeable to Ca(2+), and their currents show unique inward rectification. However, little is known about changes in the AMPAR composition and its functional significance in hypertension. In this study, we found that AMPAR-mediated EPSCs (AMPAR-EPSCs) of retrogradely labeled spinally projecting PVN neurons exhibited a linear current-voltage relationship in Wistar-Kyoto (WKY) rats. However, AMPAR-EPSCs of labeled PVN neurons in spontaneously hypertensive rats (SHR) displayed inward rectification at positive holding potentials, which were not altered by lowering blood pressure with celiac ganglionectomy. Blocking GluR2-lacking AMPARs with 1-naphthyl acetyl spermine (NAS) caused a greater reduction in the AMPAR-EPSC amplitude and firing activity of PVN neurons in SHR than in WKY rats. Furthermore, blocking NMDA receptors and inhibition of calpain or calcineurin abolished inward rectification of AMPAR-EPSCs of PVN neurons in SHR. The GluR2 protein level was significantly less in the plasma membrane but greater in the cytosolic vesicle fraction in SHR than in WKY rats. In addition, microinjection of NAS into the PVN decreased blood pressure and lumbar sympathetic nerve activity in SHR but not in WKY rats. Our study reveals that increased GluR2-lacking AMPAR activity of PVN neurons results from GluR2 internalization through NMDA receptor-calpain-calcineurin signaling in hypertension. This phenotype switch in synaptic AMPARs contributes to increased excitability of PVN presympathetic neurons and sympathetic vasomotor tone in hypertension.
|
2011 |
|
Ye, Z Y; Li, D P; Li, L; Pan, H L Protein kinase CK2 increases glutamatergic input in the hypothalamus and sympathetic vasomotor tone in hypertension Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (22), pp. 8271-8279, 2011, ISBN: 1529-2401. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat @article{RefWorks:doc:5c749951e4b02cb8b661e29d,
title = {Protein kinase CK2 increases glutamatergic input in the hypothalamus and sympathetic vasomotor tone in hypertension}, author = {Z Y Ye and D P Li and L Li and H L Pan}, doi = {10.1523/JNEUROSCI.1147-11.2011}, isbn = {1529-2401}, year = {2011}, date = {2011-06-01}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {31}, number = {22}, pages = {8271-8279}, abstract = {Increased glutamatergic input in the paraventricular nucleus (PVN) is important for high sympathetic outflow in hypertension, but the associated molecular mechanisms remain unclear. Here, we determined the role of protein kinase CK2 (formerly casein kinase II) in increased N-methyl-d-aspartate receptor (NMDAR) activity in spinally projecting PVN neurons and sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs). The selective CK2 inhibitors 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) or 4,5,6,7-tetrabromobenzotriazole (TBB) significantly decreased the frequency of miniature EPSCs (mEPSCs) of labeled PVN neurons in SHRs but not in Wistar-Kyoto (WKY) normotensive rats. Also, DRB abolished the inhibitory effect of the NMDAR antagonist AP5 on the frequency of mEPSCs in SHRs. Treatment with DRB or TBB significantly reduced the amplitude of evoked NMDA-EPSCs but not AMPA-EPSCs in SHRs. Furthermore, DRB significantly decreased the firing activity of PVN neurons in SHRs but not in WKY rats. The membrane protein level of CK2alpha in the PVN, but not brainstem and prefrontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased CK2alpha level and the effects of DRB on mEPSCs and NMDA-EPSCs. In addition, intracerebroventricular injection of DRB not only significantly reduced blood pressure and lumbar sympathetic nerve discharges but also eliminated the inhibitory effect of AP5 microinjected into the PVN on sympathetic nerve activity in SHRs. Our findings suggest that augmented CK2 activity critically contributes to increased presynaptic and postsynaptic NMDAR activity in the PVN and elevated sympathetic vasomotor tone in essential hypertension.}, keywords = {Blood Pressure, Rat}, pubstate = {published}, tppubtype = {article} } Increased glutamatergic input in the paraventricular nucleus (PVN) is important for high sympathetic outflow in hypertension, but the associated molecular mechanisms remain unclear. Here, we determined the role of protein kinase CK2 (formerly casein kinase II) in increased N-methyl-d-aspartate receptor (NMDAR) activity in spinally projecting PVN neurons and sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs). The selective CK2 inhibitors 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) or 4,5,6,7-tetrabromobenzotriazole (TBB) significantly decreased the frequency of miniature EPSCs (mEPSCs) of labeled PVN neurons in SHRs but not in Wistar-Kyoto (WKY) normotensive rats. Also, DRB abolished the inhibitory effect of the NMDAR antagonist AP5 on the frequency of mEPSCs in SHRs. Treatment with DRB or TBB significantly reduced the amplitude of evoked NMDA-EPSCs but not AMPA-EPSCs in SHRs. Furthermore, DRB significantly decreased the firing activity of PVN neurons in SHRs but not in WKY rats. The membrane protein level of CK2alpha in the PVN, but not brainstem and prefrontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased CK2alpha level and the effects of DRB on mEPSCs and NMDA-EPSCs. In addition, intracerebroventricular injection of DRB not only significantly reduced blood pressure and lumbar sympathetic nerve discharges but also eliminated the inhibitory effect of AP5 microinjected into the PVN on sympathetic nerve activity in SHRs. Our findings suggest that augmented CK2 activity critically contributes to increased presynaptic and postsynaptic NMDAR activity in the PVN and elevated sympathetic vasomotor tone in essential hypertension.
|
|
Russell, D M; McCormick, D; Taberner, A J; Malpas, S C; Budgett, D M A high bandwidth fully implantable mouse telemetry system for chronic ECG measurement Journal Article Conference proceedings : ...Annual International Conference of the IEEE Engineering in Medicine and Biology Society.IEEE Engineering in Medicine and Biology Society.Annual Conference, 2011 , pp. 7666-7669, 2011, ISBN: 1557-170X. Abstract | Links | BibTeX | Tags: ECG, Mouse @article{RefWorks:doc:5c7498efe4b0947789160e06,
title = {A high bandwidth fully implantable mouse telemetry system for chronic ECG measurement}, author = {D M Russell and D McCormick and A J Taberner and S C Malpas and D M Budgett}, doi = {10.1109/IEMBS.2011.6091889}, isbn = {1557-170X}, year = {2011}, date = {2011-01-01}, journal = {Conference proceedings : ...Annual International Conference of the IEEE Engineering in Medicine and Biology Society.IEEE Engineering in Medicine and Biology Society.Annual Conference}, volume = {2011}, pages = {7666-7669}, abstract = {We report on the development of a novel system that enables the wireless transmission of high-bandwidth physiological data from a freely moving mouse. The system employs inductive power transfer (IPT) to continuously power a battery-less transmitter using an array of overlapping planar coils placed under the animal. This arrangement provides a minimum of 20 mW at all locations and orientations across the mouse cage by selecting a coil which will sufficiently power the transmitter. Coil selection is performed by feedback control across the 2.4 GHz wireless link. A device was constructed utilizing this novel IPT system and was used to capture high-fidelity electrocardiogram (ECG) signal sampled at 2 kHz in mice. Various attributes of the ECG signal such as QT, QRS, and PR intervals could be obtained with a high degree of accuracy. This system potentially provides lifetime continuous high bandwidth measurement of physiological signals from a fully implanted telemeter in a freely moving mouse.}, keywords = {ECG, Mouse}, pubstate = {published}, tppubtype = {article} } We report on the development of a novel system that enables the wireless transmission of high-bandwidth physiological data from a freely moving mouse. The system employs inductive power transfer (IPT) to continuously power a battery-less transmitter using an array of overlapping planar coils placed under the animal. This arrangement provides a minimum of 20 mW at all locations and orientations across the mouse cage by selecting a coil which will sufficiently power the transmitter. Coil selection is performed by feedback control across the 2.4 GHz wireless link. A device was constructed utilizing this novel IPT system and was used to capture high-fidelity electrocardiogram (ECG) signal sampled at 2 kHz in mice. Various attributes of the ECG signal such as QT, QRS, and PR intervals could be obtained with a high degree of accuracy. This system potentially provides lifetime continuous high bandwidth measurement of physiological signals from a fully implanted telemeter in a freely moving mouse.
|
2010 |
|
Sawant, P M; Mountfort, D O; Kerr, D S Spectral analysis of electrocorticographic activity during pharmacological preconditioning and seizure induction by intrahippocampal domoic acid Journal Article Hippocampus, 20 (8), pp. 994-1002, 2010, ISBN: 1098-1063. Abstract | Links | BibTeX | Tags: ECG, EEG, Rat, TR50BB @article{RefWorks:doc:5c74992fe4b063d6170473a9,
title = {Spectral analysis of electrocorticographic activity during pharmacological preconditioning and seizure induction by intrahippocampal domoic acid}, author = {P M Sawant and D O Mountfort and D S Kerr}, doi = {10.1002/hipo.20698}, isbn = {1098-1063}, year = {2010}, date = {2010-08-01}, journal = {Hippocampus}, volume = {20}, number = {8}, pages = {994-1002}, abstract = {Previously we have shown that low-dose domoic acid (DA) preconditioning produces tolerance to the behavioral effects of high-dose DA. In this study, we used electrocorticography (ECoG) to monitor subtle CNS changes during and after preconditioning. Young adult male Sprague-Dawley rats were implanted with a left cortical electrode, and acute recordings were obtained during preconditioning by contralateral intrahippocampal administration of either low-dose DA (15 pmoles) or saline, followed by a high-dose DA (100 pmoles) challenge. ECoG data were analyzed by fast Fourier transformation to obtain the percentage of baseline power spectral density (PSD) for delta to gamma frequencies (range: 1.25-100 Hz). Consistent with previous results, behavioral analysis confirmed that low-dose DA preconditioning 60 min before a high-dose DA challenge produced significant reductions in cumulative seizure scores and high level seizure behaviors. ECoG analysis revealed significant reductions in power spectral density across all frequency bands, and high-frequency/high-amplitude spiking in DA preconditioned animals, relative to saline controls. Significant correlations between seizure scores and ECoG power confirmed that behavioral analysis is a reliable marker for seizure analysis. The reduction of power in delta to gamma frequency bands in contralateral cortex does not allow a clear distinction between seizure initiation and seizure propagation, but does provide objective confirmation that pharmacological preconditioning by DA reduces network seizure activity.}, keywords = {ECG, EEG, Rat, TR50BB}, pubstate = {published}, tppubtype = {article} } Previously we have shown that low-dose domoic acid (DA) preconditioning produces tolerance to the behavioral effects of high-dose DA. In this study, we used electrocorticography (ECoG) to monitor subtle CNS changes during and after preconditioning. Young adult male Sprague-Dawley rats were implanted with a left cortical electrode, and acute recordings were obtained during preconditioning by contralateral intrahippocampal administration of either low-dose DA (15 pmoles) or saline, followed by a high-dose DA (100 pmoles) challenge. ECoG data were analyzed by fast Fourier transformation to obtain the percentage of baseline power spectral density (PSD) for delta to gamma frequencies (range: 1.25-100 Hz). Consistent with previous results, behavioral analysis confirmed that low-dose DA preconditioning 60 min before a high-dose DA challenge produced significant reductions in cumulative seizure scores and high level seizure behaviors. ECoG analysis revealed significant reductions in power spectral density across all frequency bands, and high-frequency/high-amplitude spiking in DA preconditioned animals, relative to saline controls. Significant correlations between seizure scores and ECoG power confirmed that behavioral analysis is a reliable marker for seizure analysis. The reduction of power in delta to gamma frequency bands in contralateral cortex does not allow a clear distinction between seizure initiation and seizure propagation, but does provide objective confirmation that pharmacological preconditioning by DA reduces network seizure activity.
|
|
McCormick, D; Budgett, D M; Lim, M K; Vliet, Van B; Nielsen, P F; Hu, A P; Malpas, S C Frequency response of implantable blood pressure telemetry systems Journal Article Clinical and experimental pharmacology & physiology, 37 (8), pp. 862-869, 2010, ISBN: 1440-1681. Abstract | Links | BibTeX | Tags: Blood Pressure, TR43P @article{RefWorks:doc:5c7498efe4b0947789160e05,
title = {Frequency response of implantable blood pressure telemetry systems}, author = {D McCormick and D M Budgett and M K Lim and Van B Vliet and P F Nielsen and A P Hu and S C Malpas}, doi = {10.1111/j.1440-1681.2010.05406.x}, isbn = {1440-1681}, year = {2010}, date = {2010-08-01}, journal = {Clinical and experimental pharmacology & physiology}, volume = {37}, number = {8}, pages = {862-869}, abstract = {1. Measurement of blood pressure via telemetry in a variety of animal species has become an indispensable part of cardiovascular physiology, drug development and safety pharmacology. 2. These telemetry systems use fluid-filled catheters, which differ from commonly encountered indwelling catheters by virtue of their short length, high durometer, variable inner diameter and the use of a gel interface at the distal tip. 3. Despite the widespread use of blood pressure telemetry, there is little information describing the frequency response of these systems. The frequency response is of importance because it determines how well the waveform dynamics, such as pulse pressure, are captured. 4. For this reason, we measured the frequency responses of commonly used telemeters manufactured by Data Sciences International (St Paul, MN, USA; namely PA-C10, PA-C40 and PA-D70) and Telemetry Research (TR43P). The mean (+/- SEM) -3 dB frequencies measured for the PA-C10, PA-C40, PA-D70 and TR43P telemeters were 57 +/- 2 Hz, 40 +/- 6 Hz, 32 +/- 2 Hz and 173 +/- 3 Hz, respectively. 5. Simulation of the devices' dynamic performance by applying their frequency responses to a high-fidelity recording of arterial pressure demonstrated that the devices have sufficient bandwidth to accurately record arterial waveform dynamics. Experiments were also performed to determine how routine laboratory use and maintenance of the catheter affects the frequency response of the telemeters. Provided no air bubbles were introduced, these showed that the telemeters' frequency responses were robust to the maintenance procedures of tip removal and gel application. 6. The frequency response measurements, combined with simulation results, demonstrate that the systems tested have adequate dynamic performance to record arterial pressure.}, keywords = {Blood Pressure, TR43P}, pubstate = {published}, tppubtype = {article} } 1. Measurement of blood pressure via telemetry in a variety of animal species has become an indispensable part of cardiovascular physiology, drug development and safety pharmacology. 2. These telemetry systems use fluid-filled catheters, which differ from commonly encountered indwelling catheters by virtue of their short length, high durometer, variable inner diameter and the use of a gel interface at the distal tip. 3. Despite the widespread use of blood pressure telemetry, there is little information describing the frequency response of these systems. The frequency response is of importance because it determines how well the waveform dynamics, such as pulse pressure, are captured. 4. For this reason, we measured the frequency responses of commonly used telemeters manufactured by Data Sciences International (St Paul, MN, USA; namely PA-C10, PA-C40 and PA-D70) and Telemetry Research (TR43P). The mean (+/- SEM) -3 dB frequencies measured for the PA-C10, PA-C40, PA-D70 and TR43P telemeters were 57 +/- 2 Hz, 40 +/- 6 Hz, 32 +/- 2 Hz and 173 +/- 3 Hz, respectively. 5. Simulation of the devices' dynamic performance by applying their frequency responses to a high-fidelity recording of arterial pressure demonstrated that the devices have sufficient bandwidth to accurately record arterial waveform dynamics. Experiments were also performed to determine how routine laboratory use and maintenance of the catheter affects the frequency response of the telemeters. Provided no air bubbles were introduced, these showed that the telemeters' frequency responses were robust to the maintenance procedures of tip removal and gel application. 6. The frequency response measurements, combined with simulation results, demonstrate that the systems tested have adequate dynamic performance to record arterial pressure.
|
|
Huang, J; Xie, T; Wu, Y; Li, X; Lusina, S; Ji, E S; Xiang, S; Liu, Y; Gautam, S; Weiss, J W Cyclic intermittent hypoxia enhances renal sympathetic response to ICV ET-1 in conscious rats Journal Article Respiratory physiology & neurobiology, 171 (2), pp. 83-89, 2010, ISBN: 1878-1519. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c749884e4b083cef79d1b9b,
title = {Cyclic intermittent hypoxia enhances renal sympathetic response to ICV ET-1 in conscious rats}, author = {J Huang and T Xie and Y Wu and X Li and S Lusina and E S Ji and S Xiang and Y Liu and S Gautam and J W Weiss}, doi = {10.1016/j.resp.2010.03.008}, isbn = {1878-1519}, year = {2010}, date = {2010-04-01}, journal = {Respiratory physiology & neurobiology}, volume = {171}, number = {2}, pages = {83-89}, abstract = {To test the hypothesis that central changes in sympathoregulation might contribute to sympathoexcitation after cyclic intermittent hypoxia (CIH) we exposed male Sprague-Dawley rats to CIH or to room air sham (Sham) for 8h/d for 3 weeks. After completion of the exposure we assessed heart rate, mean arterial pressure and renal sympathetic nerve activity in conscious animals before and after intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 3 pmol). CIH-exposed animals had a significantly greater sympathetic response to ET-1 than did Sham-exposed animals (CIH 137.8+/-15.6% of baseline; Sham 112.2+/-10.0% of baseline; CIH vs. Sham}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } To test the hypothesis that central changes in sympathoregulation might contribute to sympathoexcitation after cyclic intermittent hypoxia (CIH) we exposed male Sprague-Dawley rats to CIH or to room air sham (Sham) for 8h/d for 3 weeks. After completion of the exposure we assessed heart rate, mean arterial pressure and renal sympathetic nerve activity in conscious animals before and after intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 3 pmol). CIH-exposed animals had a significantly greater sympathetic response to ET-1 than did Sham-exposed animals (CIH 137.8+/-15.6% of baseline; Sham 112.2+/-10.0% of baseline; CIH vs. Sham
|
2009 |
|
Huang, J; Lusina, S; Xie, T; Ji, E; Xiang, S; Liu, Y; Weiss, J W Sympathetic response to chemostimulation in conscious rats exposed to chronic intermittent hypoxia Journal Article Respiratory physiology & neurobiology, 166 (2), pp. 102-106, 2009, ISBN: 1569-9048. Abstract | Links | BibTeX | Tags: Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP @article{RefWorks:doc:5c749884e4b083cef79d1b9c,
title = {Sympathetic response to chemostimulation in conscious rats exposed to chronic intermittent hypoxia}, author = {J Huang and S Lusina and T Xie and E Ji and S Xiang and Y Liu and J W Weiss}, doi = {10.1016/j.resp.2009.02.010}, isbn = {1569-9048}, year = {2009}, date = {2009-04-01}, journal = {Respiratory physiology & neurobiology}, volume = {166}, number = {2}, pages = {102-106}, abstract = {Exposure to cyclic intermittent hypoxia (CIH) is associated with elevated arterial pressure and sustained sympathoexcitation, but the causes of the augmented sympathetic activity remain poorly understood. We recorded arterial pressure, heart rate, and renal sympathetic nerve (RSN) activity in conscious rats previously exposed to either CIH or Sham for 3 weeks during acute exposure to hypoxia (15% and 10% O(2)) or hypercapnia (7% CO(2)). Hemodynamic responses to both hypercapnia and hypoxia were similar between CIH-exposed and Sham-exposed rats, although the pattern of response was different for hypoxia (tachycardia with no change in arterial pressure) and hypercapnia (bradycardia and increased arterial pressure). RSN responses as a percent of the baseline were, however, significantly greater in CIH-exposed animals (CIH-exposed: 15% O(2) - 123.4+/-0.06%; 10% O(2) - 136.7+/-0.12%; 7% CO(2) - 138.3+/-0.18%; Sham-exposed: 15% O(2) - 106.6+/-0.03%; 10% O(2) - 107.6+/-0.01%; 7% CO(2) - 103.0+/-0.14% P<0.01 for all conditions). These data indicate that in conscious rats exposure to CIH enhances sympathetic responses to both hypoxia and hypercapnia.}, keywords = {Blood Pressure, Rat, Sympathetic Nerve Activity, TR46SP}, pubstate = {published}, tppubtype = {article} } Exposure to cyclic intermittent hypoxia (CIH) is associated with elevated arterial pressure and sustained sympathoexcitation, but the causes of the augmented sympathetic activity remain poorly understood. We recorded arterial pressure, heart rate, and renal sympathetic nerve (RSN) activity in conscious rats previously exposed to either CIH or Sham for 3 weeks during acute exposure to hypoxia (15% and 10% O(2)) or hypercapnia (7% CO(2)). Hemodynamic responses to both hypercapnia and hypoxia were similar between CIH-exposed and Sham-exposed rats, although the pattern of response was different for hypoxia (tachycardia with no change in arterial pressure) and hypercapnia (bradycardia and increased arterial pressure). RSN responses as a percent of the baseline were, however, significantly greater in CIH-exposed animals (CIH-exposed: 15% O(2) - 123.4+/-0.06%; 10% O(2) - 136.7+/-0.12%; 7% CO(2) - 138.3+/-0.18%; Sham-exposed: 15% O(2) - 106.6+/-0.03%; 10% O(2) - 107.6+/-0.01%; 7% CO(2) - 103.0+/-0.14% P<0.01 for all conditions). These data indicate that in conscious rats exposure to CIH enhances sympathetic responses to both hypoxia and hypercapnia.
|
2007 |
|
Budgett, D M; Hu, A P; Si, P; Pallas, W T; Donnelly, M G; Broad, J W; Barrett, C J; Guild, S J; Malpas, S C Novel technology for the provision of power to implantable physiological devices Journal Article Journal of applied physiology (Bethesda, Md.: 1985), 102 (4), pp. 1658-1663, 2007, ISBN: 8750-7587. Abstract | Links | BibTeX | Tags: @article{RefWorks:doc:5c74980be4b083cef79d1b7f,
title = {Novel technology for the provision of power to implantable physiological devices}, author = {D M Budgett and A P Hu and P Si and W T Pallas and M G Donnelly and J W Broad and C J Barrett and S J Guild and S C Malpas}, doi = {10.1152/japplphysiol.00105.2006}, isbn = {8750-7587}, year = {2007}, date = {2007-04-01}, journal = {Journal of applied physiology (Bethesda, Md.: 1985)}, volume = {102}, number = {4}, pages = {1658-1663}, abstract = {We report the development of a novel technology that enables the wireless transmission of sufficient amounts of power to implantable physiological devices. The system involves a primary unit generating the magnetic field and a secondary pickup unit deriving power from the magnetic field and a power conditioner. The inductively coupled system was able to supply a minimum of 20 mW at all locations and pickup orientations across a rat cage, although much higher power of up to 10 W could be achieved. We hypothesized that it would be possible to use this technology to record a high-fidelity ECG signal in a conscious rat. A device was constructed in which power was utilized to recharge a battery contained within a telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200-350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart rate changes in response to treatment with the beta blocker propranolol and the proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for up to 4 mo, and the characteristic circadian variation in heart rate was recorded. Such technology allows potentially lifetime monitoring without the need for implant refurbishment. The ability to provide suitable power levels to implanted devices without concern to the orientation of the device and without causing heating provides the basis for the development of new devices to record or influence physiological signals in animals or humans over significantly longer time periods than can currently be accommodated.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We report the development of a novel technology that enables the wireless transmission of sufficient amounts of power to implantable physiological devices. The system involves a primary unit generating the magnetic field and a secondary pickup unit deriving power from the magnetic field and a power conditioner. The inductively coupled system was able to supply a minimum of 20 mW at all locations and pickup orientations across a rat cage, although much higher power of up to 10 W could be achieved. We hypothesized that it would be possible to use this technology to record a high-fidelity ECG signal in a conscious rat. A device was constructed in which power was utilized to recharge a battery contained within a telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200-350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart rate changes in response to treatment with the beta blocker propranolol and the proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for up to 4 mo, and the characteristic circadian variation in heart rate was recorded. Such technology allows potentially lifetime monitoring without the need for implant refurbishment. The ability to provide suitable power levels to implanted devices without concern to the orientation of the device and without causing heating provides the basis for the development of new devices to record or influence physiological signals in animals or humans over significantly longer time periods than can currently be accommodated.
|
|
McCormick, D; Hu, A P; Nielsen, P; Malpas, S; Budgett, D Powering implantable telemetry devices from localized magnetic fields Journal Article Conference proceedings : ...Annual International Conference of the IEEE Engineering in Medicine and Biology Society.IEEE Engineering in Medicine and Biology Society.Annual Conference, 2007 , pp. 2331-2335, 2007, ISBN: 1557-170X. Abstract | Links | BibTeX | Tags: @article{RefWorks:doc:5c7498efe4b0947789160e07,
title = {Powering implantable telemetry devices from localized magnetic fields}, author = {D McCormick and A P Hu and P Nielsen and S Malpas and D Budgett}, doi = {10.1109/IEMBS.2007.4352793}, isbn = {1557-170X}, year = {2007}, date = {2007-01-01}, journal = {Conference proceedings : ...Annual International Conference of the IEEE Engineering in Medicine and Biology Society.IEEE Engineering in Medicine and Biology Society.Annual Conference}, volume = {2007}, pages = {2331-2335}, abstract = {This paper presents a novel method of inductively powering an implantable telemetry device over a large area. The system is based around an array of individually tuned series resonant circuits distributed across a charging pad. By varying the frequency of the driving voltage, the location of the charging field is changed. Presented are a method of controlling the resonant frequency and techniques for determining the geometry of the charging pad. Results from a nine coil system operating between 97 kHz and 209 kHz are given which can deliver 100 mW to an implanted telemeter at a height of 5cm above the charging pad.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This paper presents a novel method of inductively powering an implantable telemetry device over a large area. The system is based around an array of individually tuned series resonant circuits distributed across a charging pad. By varying the frequency of the driving voltage, the location of the charging field is changed. Presented are a method of controlling the resonant frequency and techniques for determining the geometry of the charging pad. Results from a nine coil system operating between 97 kHz and 209 kHz are given which can deliver 100 mW to an implanted telemeter at a height of 5cm above the charging pad.
|