G protein-coupled receptor kinase 4 (GRK4) gene variants, via impairment of renal dopamine receptor and enhancement of renin-angiotensin system functions, cause sodium retention and increase blood pressure.Whether or not GRK4 and the angiotensin type 1 receptor (AT1R) interact in the aorta is not known.We report that GRK4 is expressed in vascular smooth muscle cells (VSMCs) of the aorta.Heterologous expression of the GRK4 γ variant 142V in A10 cells increased AT1R protein expression and AT1R-mediated increase in intracellular calcium concentration.The increase in AT1R expression was related to an increase in AT1R mRNA expression via the NF-κ B pathway.As compared with control, cells expressing GRK4 γ 142V had greater NF-κ B activity with more NF-γ B bound to the AT1R promoter.The increased AT1R expression in cells expressing GRK4 γ 142V was also associated with decreased AT1R degradation, which may be ascribed to lower AT1R phosphorylation.There was a direct interaction between GRK4 γ wild-type (WT) and AT1R that was decreased by GRK4 γ 142V.The regulation of AT1R expression by GRK4 γ 142V in A10 cells was confirmed in GRK4 γγ 142V transgenic mice; AT1R expression was higher in the aorta of GRK4 γ 142V transgenic mice than control GRK4 γ wild-type (WT) mice.Angiotensin Ⅱ-mediated vasoconstriction of the aorta was also higher in GRK4 γ 142V than WT transgenic mice.This study provides a mechanism by which GRK4, via regulation of arterial AT1R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension.