Central Role of Gq in the Hypertrophic Signal Transduction of Angiotensin II in Vascular Smooth Muscle Cells

The angiotensin II (AngII) type 1 receptor (AT1) plays a critical role in hypertrophy of vascular smooth muscle cells (VSMCs). Although it is well known that Gq is the major G protein activated by the AT1 receptor, the requirement of Gq for AngII-induced VSMC hypertrophy remains unclear. By using cultured VSMCs, this study examined the requirement of Gq for the epidermal growth factor receptor (EGFR) pathway, the Rho-kinase (ROCK) pathway, and subsequent hypertrophy. AngII-induced intracellular Ca2+ elevation was completely inhibited by a pharmacological Gq inhibitor as well as by adenovirus encoding a Gq inhibitory minigene. AngII (100nm)-induced EGFR transactivation was almost completely inhibited by these inhibitors, whereas these inhibitors only partially inhibited AngII (100nm)-induced phosphorylation of a ROCK substrate, myosin phosphatase target subunit-1. Stimulation of VSMCs with AngII resulted in an increase of cellular protein and cell volume but not in cell number. The Gq inhibitors completely blocked these hypertrophic responses, whereas a G protein-independent AT1 agonist did not stimulate these hypertrophic responses. In conclusion, Gq appears to play a major role in the EGFR pathway, leading to vascular hypertrophy induced by AngII. Vascular Gq seems to be a critical target of intervention against cardiovascular diseases associated with the enhanced renin-angiotensin system