The Arg389GIy beta1-adrenoceptor polymorphism and catecholamine effects on plasma-renin activity

OBJECTIVES The purpose of this research was to find out whether, in humans, dobutamine-induced hemodynamic effects and increase in plasma-renin activity (PRA) might be beta(1)-adrenoceptor (beta(1)AR) genotype-dependent. BACKGROUND In vitro Arg389Gly-beta(1)AR polymorphism exhibits decreased receptor signaling. METHODS We studied 10 male homozygous Arg389-beta(1)AR subjects and 8 male homozygous Gly389 beta(1)AR subjects; to avoid influences of codon 49 polymorphism, all were homozygous Ser49-beta(1)AR. Subjects were infused with dobutamine (1 to 6 mu g/kg/min) with or without bisoprolol (10 mg orally) pretreatment, and PRA, heart rate, contractility, and blood pressure were assessed. RESULTS With regard to PRA, dobutamine increased PRA more potently in Arg389-beta(1)AR versus Gly389 beta(1)AR subjects. Bisoprolol markedly suppressed the dobutamine-induced PRA increase in Arg389- but only marginally in Gly389-beta(1)AR subjects. With regard to hemodynamics, dobutamine caused larger heart rate and contractility increases and diastolic blood pressure decreases in Arg389- versus Gly389 beta(1)AR subjects. Bisoprolol reduced dobutamine-induced heart rate and contractility increases and diastolic blood pressure decreases more potently in Arg389- versus Gly389-beta(1)AR subjects. CONCLUSIONS Codon 389 beta(1)AR polymorphism is a determinant not only of hemodynamic effects but also of PRA. Thus, beta(1)AR polymorphisms may be useful for predicting therapeutic responses to beta AR-blocker treatment.