In the hypertensive state, the expression of G protein-coupled receptor kinase 2 (GRK2) level is elevated. On the other hand, the expression of GPR30, a recently discovered GPCR is greatly impaired. The current study focuses on investigating the roles of these two proteins in regulating G protein signaling under the normal and hypertensive states. Angiotensin II and vasopressin were used to examine the effects of GRK2 on Gq coupled GPCR signaling. ERK phosphorylation was proportionally enhanced with GRK2 over-expression. On the other hand, using arborization and wrinkle assays, I have shown that GRK2 acts as a negative regulator of Gs signaling in VSMCs. Aortic ring segments were used to examine the vascular reactivity mediated by GPR30. In WKY rats, the GPR30 agonists aldostrone and G1 attenuated phenylephrine mediated vasoconstriction, while the GPR30 antagonist G15 was able to block the effects of aldosterone but not G1. A wound assay was utilized to estimate the effects of GPR30 activation on endothelial cell migration and proliferation. The G1 effect on wound healing was also seen to be GPR30 independent and EC specific. Overall, these investigations suggest that altering GRK2 expression is able to regulate both Gq and Gs signaling in VSMCs. GPR30 plays a crucial role in vascular reactivity and growth regulatory mechanisms. However, GRK2 and GPR30 do not seem to co-localized or interact in the cell
