Abstract 018: Afferent-targeted Renal Denervation Attenuates Established Deoxycorticosterone-salt Hypertension: A Central Role for Renal Afferent Nerves in Hypertension?

Abstract

Cardiovascular disease (CVD) remains the most pervasive cause of death worldwide. High arterial pressure, or hypertension (HTN), is the highest risk factor for CVD morbidity and mortality. Increased peripheral and renal sympathetic nerve activity (SNA) is hypothesized to be a primary contributor to HTN etiology. Moreover, recent clinical and experimental studies show total renal denervation (T-RDNx), may reverse the HTN; however, the contribution of afferent and efferent renal nerves in this effect is unknown. We have recently reported T-RDNx and afferent-specific denervation (A-RDNx) identically attenuated the development of deoxycorticostereone acetate (DOCA)-salt hypertension. However, the efficacy of T-RDNx and A-RDNx to reverse the established phase of this model of HTN is unknown. Therefore, the present study tested the hypothesis that A-RDNx and T-RDNx would similarly decrease the mean arterial pressure (MAP) in DOCA-salt rats with established HTN. Twenty-four male Sprague Dawley rats (275-300g) instrumented with radiotelemeters were administered DOCA (100mg, s.c.) and 0.9% saline to drink ad libitum for 35 days. On day 21 of DOCA-salt, rats underwent T-RDNx (n=9), A-RDNx (n=9), or sham (n=6) treatments. MAP was monitored for an additional 14 days. Neurogenic pressor activity (NPA) was assessed 14 days after treatment by measuring the MAP response to acute ganglionic blockade (hexamethonium, 30mg/kg, i.p.). Data was analyzed with a one-way ANOVA with Bonferroni post-hoc test (α=0.05). Data presented as mean ± SEM. MAP was similar across all groups prior to treatment on Day 21 of DOCA-salt (Sham: 165±6; T-RDNx: 164±3; A-RDNx: 162±7mmHg). Whereas Sham had no effect (-2±3) on MAP 14 days after treatment, both RDNx treatments decreased MAP by approximately 20 mmHg (T-RDNx -18±8; A-RDNx -22±5). NPA 14 days after treatment in Sham rats was -97±12mmHg. This response was reduced by nearly half in both T-RDNx (-50±9mmHg) and A-RDNx (-48±4mmHg) groups. We conclude from these findings that: 1) RDNx is effective in treating the established phase of DOCA-salt hypertension, 2) the MAP response to RDNx is mediated by ablation of afferent renal nerves, and 3) the antihypertensive response to RDNx is mediated by a decrease global neurogenic pressor activity.