Together, these molecular, cellular and physiological analyses establish that Cul4A-Gβ-mediated GRK2 degradation has a direct and important role in the regulation of heart function in male mice and that an impairment of this function, such as those seen in C825 T carriers, may contribute to the development of hypertension and weakened heart function. This evidence concerns the gene GRK2 and Hypertension.