b-Adrenergic Receptor Kinase-1 Levels in Catecholamine-Induced Myocardial Hypertrophy Regulation by b- but not a1-Adrenergic Stimulation

Pressure overload ventricular hypertrophy is accompanied by dysfunctional b-adrenergic receptor signaling due to increased levels of the b-adrenergic receptor kinase-1, which phosphorylates and desensitizes b-adrenergic receptors. In this study, we examined whether increased b-adrenergic receptor kinase 1 expression is associated with myocardial hypertrophy induced by adrenergic stimulation. With use of implanted mini-osmotic pumps, we treated mice with isoproterenol, phenylephrine, or vehicle to distinguish between a1and b-adrenergic stimulation. Both treatments resulted in cardiac hypertrophy, but only isoproterenol induced significant increases in b-adrenergic receptor kinase-1 protein levels and activity. Similarly, in isolated adult rat cardiac myocytes, 24 hours of isoproterenol stimulation resulted in a significant 2.8-fold increase in b-adrenergic receptor kinase-1 protein levels, whereas 24 hours of phenylephrine treatment did not alter b-adrenergic receptor kinase-1 expression. Our results indicate that increased b-adrenergic receptor kinase-1 is not invariably associated with myocardial hypertrophy but apparently is controlled by the state of b-adrenergic receptor activation. (Hypertension. 1999;33[part II]:396-401.)