G protein-coupled receptor kinase 4 (GRK4) gene variants or increased GRK4 expression, via impairment of renal dopamine receptor and enhancement of renin angiotensin system function, impairs renal sodium excretion, resulting in sodium retention and an increase in blood pressure. Increased aortic stiffness, a risk factor in cardiovascular disease, may be related to increased activity of the renin-angiotensin system Whether or not GRK4 and the angiotensin type 1 receptor (AT1R) interact in the aorta is not known. We now report that GRK4 is expressed in vascular smooth muscle cells (VSMCs) of the aorta. Exogenous expression of the GRK4 variant 142V in aortic A10 cells increased AT1R protein expression and AT1R-mediated increase in intracellular calcium concentration. The increased AT1R expression was caused by an increase in AT1R mRNA expression via NF-κB, because blockade of NF-κB abolished those effects of GRK4 A142V. As compared with control (vector-transfected) cells, cells expressing 142V had higher NF-kB activity and more NF-kB bound to AT1R promoter. The increased AT1R expression in cells expressing GRK4 142V was associated with decreased AT1R degradation, which was ascribed to the lower AT1R phosphorylation. There was direct interaction between GRK4 and AT1R in A10 cells which was decreased by GRK4 that could have caused the lower AT1R phosphorylation and degradation. The regulation of GRK4 of AT1R expression was confirmed in GRK4142V transgenic mice, the AT1R expression was higher, while AT1R phosphorylation was lower in aorta in GRK4 142V than control mice. Angiotensin II- mediated vasoconstriction was higher in A142V mice. This study provides a mechanism that GRK4, via regulation of arterial AT1R expression and function, engaged into the pathogenesis of hypertension.