Edothelial nitric oxide synthase inhibits G _12/13 and Rho-Kinase activated by the angiotensin II type-1 receptor implication in vascular migration

Background - Although, endothelial nitric oxide (NO) synthase (eNOS) is believed to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1 receptor, the exact signaling mechanism remains unclear. Methods and Results - By expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we investigated a signal transduction mechanism of the eNOS gene transfer in preventing vascular remodeling induced by AngII. We found marked inhibition of Angll-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS gene transfer whereas G _q-dependent transactivation of the epidermal growth factor receptor by AngII remains intact. This could be explained by the specific inhibition of G _12/13 activation by eNOS-mediated G _12/13 phosphorylation. Conclusion - The eNOS/NO cascade specifically targets the Rho/Rho-kinase system via inhibition of G _12/13 to prevent vascular migration induced by AngII, representing a novel signal cross-talk in cardiovascular protection by NO.