Intermittent electrical stimulation of the right cervical vagus nerve in salt-sensitive hypertensive rats: effects on blood pressure, arrhythmias, and ventricular electrophysiology

Abstract

Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases.

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

“…HFpEF is characterized by autonomic imbalance with increased sympathetic nerve activity, which is closely associated with diastolic dysfunction (Aikawa et al., ; Grassi et al., ), while clinical studies have shown that sympathetic hyperactivity contributes to the development of diastolic dysfunction in patients with hypertension and to disease progression in patients with HFpEF (Florea & Cohn, ). Consistent with our results, a recent study revealed that right cervical VNS decreased sympathetic activity and attenuated the HS diet‐induced increase of BP in DS rats (Annoni et al., ). The mechanism of this effect involves inhibition of central sympathetic outflow (Annoni et al., ).…”

“…Consistent with our results, a recent study revealed that right cervical VNS decreased sympathetic activity and attenuated the HS diet‐induced increase of BP in DS rats (Annoni et al., ). The mechanism of this effect involves inhibition of central sympathetic outflow (Annoni et al., ). We, and others, have previously shown that VNS, even at subthreshold levels not causing bradycardia, exerted antiadrenergic effects, by injuring the sympathetic neurons in the stellate ganglia (Chinda et al., ; Sha et al., ).…”

Vagus Nerve Stimulation Ameliorates L-NAME-induced Preeclampsia-like Symptoms in Rats Through Inhibition of the Inflammatory Response

“…The effectiveness of VNS's blood pressure-lowering effects depends on several factors, including the stimulus parameters, position, administration route, and experimental model. 29 VNS also increases the levels of nitric oxide, the major vasodilator in the circulation, thereby improving endothelial function and reducing vascular resistance, 30 which suggests that lower peripheral resistance may lead to reduced blood pressure in response to VNS treatment. In addition, our data further demonstrated that MLA failed to block the effect of VNS on the lower heart rate in VNS-treated animals.…”

Vagus Nerve Stimulation for Blood Pressure and Heart Rate Regulation

“…To simulate BP and HR VNS responses, we developed a model using both human [4,8,9] and murine [11,12] BP, HR and VNS treatment parameters, and an analog simulation format based on Fig. 1, to reveal stable and unstable responses, state-of-the-heart transitions, and responses to simulated therapeutic inputs.…”