Transgenic Expression of CGRP Receptor Subunit RAMP1 in Nervous System Improves Autonomic Regulation and Prevents Angiotensin II Hypertension

We demonstrated recently that mice with ubiquitous, widespread over expression of R eceptor A ctivity‐ M odifying P rotein‐ 1 (RAMP1), an obligatory subunit of the calcitonin gene‐related peptide (CGRP) receptor, exhibit increased baroreflex sensitivity (BRS) and resistance to angiotensin II (AngII)‐induced hypertension [Hypertension 2010] . In the present study, we tested the hypothesis that nervous system CGRP receptors mediate these protective effects. Blood pressure (BP) and heart rate (HR) were measured by telemetry in Nestin/hRAMP1 transgenic mice (n=5) with human RAMP1 targeted to the nervous system and littermate control mice (n=4) [Zhang et al., J Neurosci 2007] , before and during Day 7 of AngII infusion (osmotic minipump, 1000 ng/kg/min). hRAMP1 expression was detected in nervous system but not in heart, kidneys and stomach of Nestin/hRAMP1 mice. In control mice, AngII infusion increased BP, and decreased HR variability (HRV) and BRS (sequence technique) (Table, AngII vs. baseline, * P<0.05). These deleterious effects of AngII were abrogated in Nestin/hRAMP1 mice (Table, Nestin/hRAMP1 vs. controls, † P<0.05). We conclude that Nestin/hRAMP1 mice are resistant to AngII‐induced autonomic dysregulation and hypertension. The results suggest that the antihypertensive and autonomic actions of CGRP are mediated via CGRP receptors in the nervous system. (AHA 0855944G, HL14388, VA)