Abstract P315: Angiotensin Ii Type 1a Receptor Expressed In Smooth Muscle Cells Is Required For Vascular Remodeling In Mice Infused With Angiotensin II

Abstract

Angiotensin II (AngII) type 1A (AT 1A ) receptors play a critical role in hypertension and cardiovascular remodeling in mice infused with AngII. Although vascular remodeling, a significant contributor to organ damage, occurs concurrently with hypertension in AngII infused mice, the contribution of smooth muscle AT 1A in this process remains unexplored. Accordingly, it is hypothesized that smooth muscle AT 1A receptors exclusively contribute to both medial thickening and adventitial fibrosis regardless of the presence of hypertension. 1 μg/kg/min AngII was infused for 2 weeks in two distinct AT 1A receptor silenced mice, knock-in Tagln -mediated constitutive smooth muscle AT 1A receptor silenced mice and Myh11 -mediated inducible smooth muscle AT 1A silenced mice for evaluation of hypertensive cardiovascular remodeling. Medial thickness, adventitial collagen deposition and immune cell infiltration in aorta were increased in control mice but not in both smooth muscle AT 1A receptor silenced mice. Coronary arterial perivascular fibrosis in response to AngII infusion was also attenuated in both AT 1A receptor silenced mice. AngII-induced cardiac hypertrophy was attenuated in constitutive smooth muscle AT 1A receptor silenced mice. However, AngII-induced cardiac hypertrophy and hypertension were not altered in inducible smooth muscle AT 1A receptor silenced mice (SBP control 148 vs knockout 149 mmHg). In conclusion, smooth muscle AT 1A receptors mediate AngII-induced vascular remodeling including medial hypertrophy and inflammatory perivascular fibrosis regardless of the presence of hypertension. Our data suggest an independent etiology of blood pressure elevation and hypertensive vascular remodeling in response to AngII.