Subdiaphragmatic Vagal Nerve Stimulation Attenuates the Development of Hypertension and Alters NTS Transcriptional Networks in the SHR

Augmented vagal signaling may be therapeutic in hypertension. Most studies to date employed stimulation of the cervical vagal branches. Here, we investigated the effects of chronic intermittent electric stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on long term blood pressure (BP), immune markers, and gut microbiota in the spontaneously hypertensive rat (SHR), a rodent model of hypertension characterized by vagal dysfunction, gut dysbiosis and low-grade inflammation. We evaluated the effects of sdVNS on transcriptional networks in the nucleus of the solitary tract (NTS), a major cardioregulatory brain region with direct gut vagal projections. Male juvenile SHR were implanted with radiotelemetry transmitters and vagal nerve cuffs for chronic intermittent electric sdVNS, applied three times per day for seven consecutive weeks followed by one week of no stimulation. BP was measured once a week using telemetry in the sdVNS group as well as the age-matched Sham-stimulated SHR controls. At endpoint, colonic and circulating inflammatory markers and corticosterone, and circulating catecholamines were investigated. Bacterial 16s sequencing measured gut bacterial abundance and composition. RNAseq evaluated the effects of sdVNS on transcriptional networks in the NTS. SHRs that received sdVNS exhibited attenuated development of hypertension compared to the Sham. No changes in peripheral inflammatory markers, corticosterone or catecholamines, and no major differences in gut bacterial diversity and composition were observed following sdVNS, apart from decreased abundance of Defluviitaleaceale bacterium detected in the sdVNS SHR compared to the Sham. RNAseq revealed significant sdVNS-dependent modulation of select NTS transcriptional networks, including catecholaminergic and corticosteroid networks.