Electrical Stimulation of Sub-Diaphragmatic Vagal Trunk Alleviates Hypertension in the SHR

Introduction: The vagus facilitates a bidirectional gut-brain communication. Low vagal tone is shown in conditions marked by inflammation and dysbiosis, including hypertension (HTN). However, the role of gut-projecting vagal nerve branches in blood pressure (BP) control is unexplored. Supplementing the potentially impaired gut vagal tone using electrical vagal nerve stimulation (vns) may restore homeostasis of the microbiota-gut-brain axis in HTN. Methods: Male 8 week-old Wistar-Kyoto (WKY, N=6) and spontaneously hypertensive rats (SHR, N=10) were used. Rats were implanted with radiotelemetric BP transducers. WKY rats received either a unilateral surgical vagotomy of the ventral sub-diaphragmatic vagal trunk (vgnx, N=3) or sham surgery (SHAM, N=3). SHR were implanted with either a silicone cuff electrode (500μm, Microprobes for Life Sciences, Gaithersburg, MD) (vns, N=5) or a sham cuff (SHAM, N=5) on same vagal trunk. SHR were connected to an IZ2H current controlled stimulus generator (Tucker-Davis Technologies, Alachua, FL), and subjected to biphasic, 600μA, 0.5s/phase, 25Hz vns for 10 minutes per session, three sessions per day, 5 days per week. 24-hour BP recordings were made once per week for seven weeks in all rats. Relative abundance of gut bacterial phyla ( Firmicutes, Bacteriodetes, Actinobacteria ) was determined in fecal DNA of all rats using qPCR. Results: Compared with SHAM, WKY vgnx showed a significant elevation in systolic BP (SBP) at week 7 post-vgnx (WKY SHAM: 148±4 mm Hg vs. WKY vgnx: 177±4 mm Hg; p <0.05). After 7 weeks of vns, SHR STIM group exhibited a significant dampening in SBP rise from baseline (SHR SHAM: ΔSBP=44±5 mm Hg vs. SHR vns: 22±3 mm Hg; p <0.05) and in mean BP (MBP) rise from baseline (SHR SHAM: ΔMBP=38±4 mm Hg vs. SHR vns: 14±3 mm Hg; p <0.05) compared to SHAM. No difference was observed in relative abundance of major bacterial phyla between the WKY vgnx and SHR vns rats and their respective controls. Conclusions: Bioelectric restoration of gut vagal tone is beneficial in restitution of neural gut-brain axis in control of BP in HTN. Considering no changes were observed in major gut bacterial phyla following WKY vgnx and SHR vns, the observed BP responses may be due to perturbations in gut vagal afferent rather than efferent signaling.