Central Sympathoinhibition Abrogates Angiotensin II‐induced Autonomic Dysregulation, Hypertension and Blood Pressure Variability in Control and Methionine Sulfoxide Reductase‐A Deficient Mice

Abstract

We recently reported that mice deficient in methionine sulfoxide reductase-A (MsrA), a unique antioxidant, exhibit sympathovagal imbalance and exacerbation of angiotensin II (Ang II)-induced hypertension. In this study, we tested the hypothesis that central administration of the sympathoinhibitory drug rilmenidine (RIL) will improve autonomic regulation and abrogate the enhanced Ang II-induced hypertension in MsrA-/- mice. Blood pressure (BP) and heart rate (HR) were measured in control C57BL/6 (n=7) and MsrA-/- (n=8) mice by telemetry, before and during four weeks of Ang II infusion (1000ng/kg/min). Subgroups of mice were infused ICV with RIL (42 ng/g/hr, n=4) over the last 2 weeks of Ang II infusion. As expected, RIL profoundly inhibited sympathetic tone (HR response to propranolol) in Ang II-infused C57BL/6 and MsrA-/- mice (Table). RIL reversed hypertension (Table) and increased vagal tone and baroreflex sensitivity (sequence technique) in both groups of mice. Moreover, enhanced Ang II-induced increases in BP and BP variability (BPV, SD of systolic BP) in MsrA-/- mice were abolished by RIL (Table). We conclude that targeting excessive sympathetic activity with sustained infusion of RIL abrogates Ang II-induced autonomic dysregulation, hypertension, and BPV. (HL14388, VA)