β-Adrenergic receptor kinase-1 levels in catecholamine-induced myocardial hypertrophy: Regulation by β- but not α₁-adrenergic stimulation

Pressure overload ventricular hypertrophy is accompanied by dysfunctional β-adrenergic receptor signaling due to increased levels of the β-adrenergic receptor kinase-1, which phosphorylates and desensitizes β- adrenergic receptors. In this study, we examined whether increased β- 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 α₁- and β-adrenergic stimulation. Both treatments resulted in cardiac hypertrophy, but only isoproterenol induced significant increases in β-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 β-adrenergic receptor kinase-1 protein levels, whereas 24 hours of phenylephrine treatment did not alter β-adrenergic receptor kinase-1 expression. Our results indicate that increased β-adrenergic receptor kinase-1 is not invariably associated with myocardial hypertrophy but apparently is controlled by the state of β-adrenergic receptor activation.