Abstract 17534: Afferent Vagal Nerve Stimulation Dose Dependently Inhibits Sympathetic Nerve Activity Through the Resetting of Baroreflex Central Arc

Abstract

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.