Beta‐arrestin and vasomotor control in the spontaneously hypertensive rat

Abstract

We tested the hypothesis that spontaneously hypertensive rats (SHR) exhibit reduced desensitization of the neuropeptide Y (NPY) Y1 receptor (Y1R) leading to altered hindlimb vasomotor control. ?‐arrestin 2 ( ?‐arr) is a key regulatory protein involved in the desensitization of the Y1R (as well as many other G‐protein coupled receptors (GPCRs)). Reduced ?‐arr would lead to less desensitization, and prolonged signal transduction. In vivo measurements of arterial pressure and femoral blood flow (Transonic) were measured in 7‐week old anaesthesized male SHR animals (n=5) and their genetic control (WKY; n=6) rats. Red vastus lateralis from the animals were analyzed for ?‐arr content by western blotting techniques. SHR content of ?‐arr was 1412 ± 827 units while ?‐arr content in the WKY animals was 3546 ± 898 units (p = 0.003; mean ± SD). These data are consistent with the 55% (p = 0.07) and 60% (p = 0.06) reductions in both hindlimb blood flow (ml/min) and conductance (ml/min/mmHg) to exogenous NPY (r = 0.77, p = 0.02 and r = 0.66, p = 0.05 respectively). β‐arr was also correlated with reductions in hindlimb flow to exogenous phenylephrine (r =0.76, p = 0.02). These data implicate a role for β‐arr in Y1R and alpha adrenergic receptor sensitization in hypertension. This work was supported by CIHR.