Afferent Vagal Nerve Stimulation Resets the Baroreflex Neural Arc and Inhibits Sympathetic Nerve Activity

Background: Arterial baroreflex is a powerful regulator of the sympathetic nerve activity (SNA) and arterial pressure (AP). Although vagal nerve stimulation (VNS) has been developed as a neuro-modulatory therapy for heart failure, the impact of VNS on baroreflex and SNA remains unknown. Since the afferent fibers of vagal nerves and of baroreceptors converge in the nucleus tractus solitarii, we investigated how the selective afferent VNS (AVNS) impacts on baroreflex in regulating SNA and AP. Methods: We used 6 anesthetized Sprague-Dawley rats (530±11g). We vascularly isolated bilateral carotid sinuses and servo-controlled intra-sinus pressure (CSP). We measured AP, CSP and splanchnic SNA simultaneously. We attached an electrode to the vagal nerve. We established the baseline intensity (voltage) of VNS that reduced heart rate by 10-20%. We then sectioned the vagal nerve at the caudal side of the electrode. We conducted AVNS at 3 doses, baseline, 2xbaseline and 4xbaseline. We changed CSP stepwise from 60 to 160mmHg to analyze static baroreflex function with/without AVNS. To estimate dynamic baroreflex function, we perturbed CSP using binary random sequence (mean AP±20mmHg) and compared the transfer functions (TF) with/without AVNS. Results: AVNS dose-dependently shifted the CSP-SNA relation downward (p<0.05, Fig. 1) without changing the maximum gain, while did not affect the SNA-AP relation (Fig. 2). The TF of CSP-SNA relation approximated a high pass filter characteristics. AVNS dose-dependently decreased the dynamic gain (Control: 0.72±0.20, baseline: 0.46±0.14, 2xbaseline: 0.38±0.12, 4xbaseline: 0.20±0.08 %/mmHg, p<0.05), whereas did not affect the TF of SNA-AP relation. Conclusions: AVNS dose-dependently suppresses SNA by resetting the static CSP-SNA relation, i.e., the baroreflex central arc. However, AVNS reduces the dynamic gain of baroreflex central arc. We conclude that AVNS lowers SNA at the expense of compromising dynamic AP stabilization.

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Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy

Heart Rhythm ◽

10.1016/j.hrthm.2017.07.035 ◽

2017 ◽

Vol 14 (12) ◽

pp. 1771-1778 ◽

Cited By ~ 16

Author(s):

Yuan Yuan ◽

Jonathan L. Hassel ◽

Anisiia Doytchinova ◽

David Adams ◽

Keith C. Wright ◽

...

Keyword(s):

Nerve Stimulation ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Vagal Nerve ◽

Vagal Nerve Stimulation ◽

Drug Resistant ◽

Nerve Activity ◽

Skin Sympathetic Nerve Activity ◽

Drug Resistant Epilepsy

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Is there a central nervous system component to acute baroreflex resetting in rats?

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.262.2.h503 ◽

1992 ◽

Vol 262 (2) ◽

pp. H503-H510 ◽

Cited By ~ 2

Author(s):

C. M. Heesch ◽

K. W. Barron

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nerve Stimulation ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

System Component ◽

Nerve Activity ◽

Linear Portion ◽

Aortic Nerve ◽

Maximum Inhibition

This study was designed to evaluate a possible central nervous system (CNS) component to acute baroreflex resetting. In nine arterial baroreceptor-denervated, chloralose-urethan-anesthetized rats, a control (C) aortic nerve stimulation curve (3-5 V, 1 ms, 0-64 Hz) was obtained. Next, a constant "baroreceptor" input was delivered to the CNS (left aortic nerve stimulation, 10 min, 10.2 +/- 1.5 Hz). Within the first 13 s of aortic nerve stimulation, maximum inhibition of lumbar sympathetic nerve activity (LSNA) was 60 +/- 7.8% of baseline and at 1 min it increased to 68 +/- 5.6% of baseline. At the end of the 10-min aortic nerve stimulation, LSNA was not different from the response at 1 min (68 +/- 5.6% = 74 +/- 4.1%). Immediately after the constant stimulation (within 30 s), a test or reset (RS) curve was obtained (0-64 Hz). A recovery (RC) curve was obtained 10-20 min later. The slope of the linear portion of the curve and the stimulation frequency that produced 50% maximum inhibition (ES50) were compared among the three baroreflex curves (C, RS, RC,) and no significant differences were found. Thus, although a CNS component to baroreflex adaptation was evident during the first minute of aortic nerve stimulation, a longer term acute resetting of the baroreflex curve did not occur.

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Arteriolar wall Po 2 and nitric oxide release during sympathetic vasoconstriction in the rat intestine

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.2.h484 ◽

2000 ◽

Vol 279 (2) ◽

pp. H484-H491 ◽

Cited By ~ 11

Author(s):

Bryan A. Sauls ◽

Matthew A. Boegehold

Keyword(s):

Nitric Oxide ◽

Nerve Stimulation ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Rat Intestine ◽

Nerve Activity ◽

Sympathetic Nerve Stimulation ◽

Nitric Oxide Release ◽

Sympathetic Vasoconstriction ◽

Arteriolar Wall

Endothelium-derived nitric oxide (NO) attenuates arteriolar constriction in the rat small intestine during periods of increased sympathetic nerve activity. This study was undertaken to test the hypothesis that a flow-dependent fall in arteriolar wall Po 2 serves as the stimulus for endothelial NO release under these conditions. Sympathetic nerve stimulation at 3–16 Hz induced frequency-dependent arteriolar constriction, with arteriolar wall O2 tension (Po 2) falling from 67 ± 3 mmHg to as low as 41 ± 6 mmHg. Arteriolar responses to nerve stimulation were enhanced after inhibition of NO synthase with N G-monomethyl-l-arginine (l-NMMA). Under a high-O2 (20%) superfusate, the fall in wall Po 2 was significantly attenuated, arteriolar constrictions were increased by 57 ± 9 to 66 ± 12%, and these responses were no longer sensitive tol-NMMA. The high-O2 superfusate had no effect on vascular smooth muscle responsiveness to NO (as judged by arteriolar responses to sodium nitroprusside) or on arteriolar wall oxidant activity (as determined by the reduction of tetranitroblue tetrazolium dye). These results indicate that a flow-dependent fall in arteriolar wall Po 2 may serve as a stimulus for the release of endothelium-derived NO during periods of increased sympathetic nerve activity.

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Low Pressure Baroreflex Evokes Biphasic Change in Sympathetic Nerve Activity through Vagal Nerve

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2013.08.420 ◽

2013 ◽

Vol 19 (10) ◽

pp. S161

Author(s):

Yasuhiro Oga ◽

Takuya Kishi ◽

Keita Saku ◽

Takamori Kakino ◽

Masataka Ikeda ◽

...

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Low Pressure ◽

Vagal Nerve ◽

Nerve Activity

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Subcutaneous nerve stimulation reduces sympathetic nerve activity in ambulatory dogs with myocardial infarction

Heart Rhythm ◽

10.1016/j.hrthm.2020.02.006 ◽

2020 ◽

Vol 17 (7) ◽

pp. 1167-1175

Author(s):

Yuan Yuan ◽

Ye Zhao ◽

Johnson Wong ◽

Wei-Chung Tsai ◽

Zhaolei Jiang ◽

...

Keyword(s):

Myocardial Infarction ◽

Nerve Stimulation ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Nerve Activity

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Low-frequency oscillation of sympathetic nerve activity decreases during development of tilt-induced syncope preceding sympathetic withdrawal and bradycardia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01027.2004 ◽

2005 ◽

Vol 289 (4) ◽

pp. H1758-H1769 ◽

Cited By ~ 47

Author(s):

Atsunori Kamiya ◽

Junichiro Hayano ◽

Toru Kawada ◽

Daisaku Michikami ◽

Kenta Yamamoto ◽

...

Keyword(s):

Heart Rate ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Low Frequency ◽

Vagal Nerve ◽

Low Frequency Oscillation ◽

Nerve Activity ◽

Neurally Mediated Syncope ◽

Severe Hypotension ◽

Vagal Nerve Activity

Sympathetic activation during orthostatic stress is accompanied by a marked increase in low-frequency (LF, ∼0.1-Hz) oscillation of sympathetic nerve activity (SNA) when arterial pressure (AP) is well maintained. However, LF oscillation of SNA during development of orthostatic neurally mediated syncope remains unknown. Ten healthy subjects who developed head-up tilt (HUT)-induced syncope and 10 age-matched nonsyncopal controls were studied. Nonstationary time-dependent changes in calf muscle SNA (MSNA, microneurography), R-R interval, and AP (finger photoplethysmography) variability during a 15-min 60° HUT test were assessed using complex demodulation. In both groups, HUT during the first 5 min increased heart rate, magnitude of MSNA, LF and respiratory high-frequency (HF) amplitudes of MSNA variability, and LF and HF amplitudes of AP variability but decreased HF amplitude of R-R interval variability (index of cardiac vagal nerve activity). In the nonsyncopal group, these changes were sustained throughout HUT. In the syncopal group, systolic AP decreased from 100 to 60 s before onset of syncope; LF amplitude of MSNA variability decreased, whereas magnitude of MSNA and LF amplitude of AP variability remained elevated. From 60 s before onset of syncope, MSNA and heart rate decreased, index of cardiac vagal nerve activity increased, and AP further decreased to the level at syncope. LF oscillation of MSNA variability decreased during development of orthostatic neurally mediated syncope, preceding sympathetic withdrawal, bradycardia, and severe hypotension, to the level at syncope.

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