SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2∙-), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions ofO2∙-may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function.

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Comparison of phenylephrine bolus and infusion methods in baroreflex measurements

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.3.962 ◽

1990 ◽

Vol 69 (3) ◽

pp. 962-967 ◽

Cited By ~ 27

Author(s):

J. T. Sullebarger ◽

C. S. Liang ◽

P. D. Woolf ◽

A. E. Willick ◽

J. F. Richeson

Keyword(s):

Heart Rate ◽

Arterial Pressure ◽

Baroreflex Sensitivity ◽

Heart Rate Response ◽

Pressor Response ◽

Plasma Catecholamines ◽

Systolic Arterial Pressure ◽

Normal Subjects ◽

Vagus Nerves ◽

Baroreflex Control

Phenylephrine (PE) bolus and infusion methods have both been used to measure baroreflex sensitivity in humans. To determine whether the two methods produce the same values of baroreceptor sensitivity, we administered intravenous PE by both bolus injection and graded infusion methods to 17 normal subjects. Baroreflex sensitivity was determined from the slope of the linear relationship between the cardiac cycle length (R-R interval) and systolic arterial pressure. Both methods produced similar peak increases in arterial pressure and reproducible results of baroreflex sensitivity in the same subjects, but baroreflex slopes measured by the infusion method (9.9 +/- 0.7 ms/mmHg) were significantly lower than those measured by the bolus method (22.5 +/- 1.8 ms/mmHg, P less than 0.0001). Pretreatment with atropine abolished the heart rate response to PE given by both methods, whereas plasma catecholamines were affected by neither method of PE administration. Naloxone pretreatment exaggerated the pressor response to PE and increased plasma beta-endorphin response to PE infusion but had no effect on baroreflex sensitivity. Thus our results indicate that 1) activation of the baroreflex by the PE bolus and infusion methods, although reproducible, is not equivalent, 2) baroreflex-induced heart rate response to a gradual increase in pressure is less than that seen with a rapid rise, 3) in both methods, heart rate response is mediated by the vagus nerves, and 4) neither the sympathetic nervous system nor the endogenous opiate system has a significant role in mediating the baroreflex control of heart rate to a hypertensive stimulus in normal subjects.

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Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3

BioMed Research International ◽

10.1155/2014/709159 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Ching-Feng Cheng ◽

Terry B. J. Kuo ◽

Wei-Nan Chen ◽

Chao-Chieh Lin ◽

Chih-Cheng Chen

Keyword(s):

Heart Rate ◽

Autonomic Function ◽

Physiological Role ◽

Autonomic Regulation ◽

Pcr Analysis ◽

Baseline Heart Rate ◽

Cardiac Autonomic Function ◽

Sympathetic Function ◽

Cardiac Autonomic Regulation

Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function usingAsic3−/−mice.Asic3−/−mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore,Asic3−/−mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found inAsic3−/−mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

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Effect of vasopressin and phenylephrine on arterial pressure and heart rate in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.251.2.h253 ◽

1986 ◽

Vol 251 (2) ◽

pp. H253-H260

Author(s):

J. L. Robinson

Keyword(s):

Heart Rate ◽

Arterial Pressure ◽

Response Curve ◽

Baroreflex Sensitivity ◽

Conscious Dogs ◽

Baroreflex Control ◽

Pressure Stimulus ◽

Before And After ◽

Autonomic Receptors ◽

The Difference

The effect of arginine vasopressin (AVP) and phenylephrine (PE) infusions on mean arterial pressure (MAP) and heart rate (HR) were compared in conscious dogs with all autonomic receptors intact (I), during muscarinic blockade (MB) and during ganglionic blockade (GB). After either MB or GB, the dose-MAP response curve for AVP and PE was shifted to the left of the I response curve; a greater shift was observed with AVP than with PE. The MAP threshold after GB for AVP and PE occurred at 10 and 50% of the threshold dose observed during the I response, respectively. Not only did the MAP threshold occur at a lower dose after MB and GB, but also the slope of the response curve was steeper than that of the I response. Comparing the amount of drug necessary to increase MAP 25 mmHg above control for PE and AVP before and after GB, the intact PE response required 4.3 +/- 1.0 (P less than 0.01) times more drug than during GB versus the intact AVP required 16.8 +/- 2.8 (P less than 0.01) times more drug than during GB. The baroreflex control of HR when all receptors were intact was 3.4 +/- 0.4 (P = 0.001) times more sensitive during AVP compared with PE; no differences were observed after MB. There were no significant changes in HR to AVP or PE after GB, thus indicating a lack of a direct effect of these agents on the HR. Our results show that MB and GB equally potentiate the pressor effects of AVP and PE, and the augmentation was much greater for AVP than for PE. The difference in the potentiation of these two vasoconstrictors is consistent with the finding that the baroreflex sensitivity during AVP was enhanced compared with PE. We have postulated that, in the resting conscious dog, AVP increases the sensitivity of the baroreflex primarily by producing a greater level of parasympathetic tone to the heart in response to a given pressure stimulus.

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Heart-rate variability and cardiac autonomic function in diabetes

Diabetes ◽

10.2337/diabetes.39.10.1177 ◽

1990 ◽

Vol 39 (10) ◽

pp. 1177-1181 ◽

Cited By ~ 41

Author(s):

S. C. Malpas ◽

T. J. Maling

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Autonomic Function ◽

Cardiac Autonomic Function

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Compensatory recovery of parasympathetic control of heart rate after unilateral vagotomy in rabbits

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.262.4.h1122 ◽

1992 ◽

Vol 262 (4) ◽

pp. H1122-H1127 ◽

Cited By ~ 1

Author(s):

D. D. Lund ◽

G. A. Davey ◽

A. R. Subieta ◽

B. J. Pardini

Keyword(s):

Heart Rate ◽

Arterial Pressure ◽

Nerve Stimulation ◽

Vagal Stimulation ◽

Acetylcholinesterase Inhibition ◽

Baroreflex Control ◽

Recovery Mechanism ◽

Vagal Innervation ◽

Increased Sensitivity ◽

Parasympathetic Control

Compensatory recovery by the intact vagal innervation after unilateral vagotomy was investigated by measuring parasympathetic-mediated control of heart rate in beta-adrenergic-blocked rabbits. Direct contralateral vagal nerve stimulation produced greater bradycardia in anesthetized rabbits with chronic vagotomy compared with acutely vagotomized controls. Vagal stimulation during acetylcholinesterase inhibition by physostigmine and direct neuroeffector stimulation by methacholine indicated that a change in metabolism of the neurotransmitter or an increased sensitivity of the tissue to acetylcholine were not responsible for augmentation of vagal responses. Baroreflex control of heart rate in response to an increase in arterial pressure was also tested in urethan-anesthetized rabbits. There was a significant reduction in the prolongation of the R-R interval during baroreflex activation acutely after midcervical vagotomy. These values were subsequently above control levels in rabbits 28 days after vagotomy. In conscious rabbits, the decrease in baroreflex control of heart rate progressively recovered to control levels within 6 days. These results suggest that the recovery mechanism after unilateral vagotomy may be related to peripheral and central compensatory changes in the intact contralateral vagus nerve.

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Impact of Menstrual Cycle on Cardiac Autonomic Function Assessed by Heart Rate Variability and Heart Rate Recovery

Medical Principles and Practice ◽

10.1159/000444322 ◽

2016 ◽

Vol 25 (4) ◽

pp. 374-377 ◽

Cited By ~ 14

Author(s):

Şadan Yazar ◽

Mehmet Yazıcı

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Menstrual Cycle ◽

Autonomic Function ◽

Heart Rate Recovery ◽

Cardiac Autonomic Function

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Isoflurane Depresses Baroreflex Control of Heart Rate in Decerebrate Rats

Anesthesiology ◽

10.1097/00000542-200205000-00026 ◽

2002 ◽

Vol 96 (5) ◽

pp. 1214-1222 ◽

Cited By ~ 24

Author(s):

Jong S. Lee ◽

Don Morrow ◽

Michael C. Andresen ◽

Kyoung S. K. Chang

Keyword(s):

Central Nervous System ◽

Heart Rate ◽

Nervous System ◽

Baroreflex Sensitivity ◽

Baroreflex Control ◽

Beta Adrenoceptor ◽

Reflex Bradycardia ◽

Reflex Tachycardia ◽

Map Data ◽

Regulatory Sites

Background Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. Methods The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. Results Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. Conclusions Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.

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Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00852.2004 ◽

2006 ◽

Vol 290 (4) ◽

pp. R1027-R1034 ◽

Cited By ~ 35

Author(s):

Andréia C. Alzamora ◽

Robson A. S. Santos ◽

Maria J. Campagnole-Santos

Keyword(s):

Heart Rate ◽

Baroreflex Sensitivity ◽

Opposite Effect ◽

Ventrolateral Medulla ◽

Ang Ii ◽

Differential Modulation ◽

Baroreflex Control ◽

Caudal Ventrolateral Medulla ◽

Angiotensin Peptides ◽

Reflex Bradycardia

We determined the effect of microinjection of ANG-(1–7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1–7) and ANG II (25 pmol) after RVLM microinjection (11 ± 0.8 and 10 ± 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1–7) and ANG II produced hypotension (−11 ± 1.5 and −11 ± 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1–7) attenuated the baroreflex bradycardia (0.26 ± 0.06 ms/mmHg vs. 0.42 ± 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 ± 0.19 ms/mmHg vs. 0.42 ± 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 ± 0.06 ms/mmHg vs. 0.31 ± 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 ± 0.16 ms/mmHg vs. 0.41 ± 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1–7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1–7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart.

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