Smooth muscle cell specific deletion of the PKGIα target RGS2 induces vascular dysfunction and hypertension

Introduction Current dogma regarding the etiology of hypertension states that renal abnormalities of sodium handling cause an increase in blood volume that overwhelms vascular counter-regulatory responses, resulting in hypertension. Although it is known that acute changes in vascular morphology and tone can cause an increase in vascular resistance and blood pressure, we have hypothesized that primary abnormalities of the regulation of vascular smooth muscle tone can also be an etiology for hypertension. We have previously demonstrated that disruption of the leucine zipper targeting domain in PKGIa results in dysregulation of vasomotor tone and hypertension in the setting of normal renal function. To directly test the hypothesis that abnormalities in vasomotor regulation can be the primary etiology of hypertension, we have developed and now characterize a novel mouse model harboring a smooth muscle cell (SMC) specific deletion of the PKGIa target we identified previously, RGS2, a GTPase activating protein that inhibits Gq-coupled G-protein coupled receptor (GPCR) signaling, whose total body deletion in mice causes hypertension (Tang et al, Nature Medicine, 2003).