The Arg389Gly Beta1-Adrenoceptor Polymorphism and Catecholamine Effects on Plasma-Renin Activity

ObjectivesThe purpose of this research was to find out whether, in humans, dobutamine-induced hemodynamic effects and increase in plasma-renin activity (PRA) might be beta1-adrenoceptor (β1AR) genotype-dependent.BackgroundIn vitro Arg389Gly-β1AR polymorphism exhibits decreased receptor signaling.MethodsWe studied 10 male homozygous Arg389-β1AR subjects and 8 male homozygous Gly389β1AR subjects; to avoid influences of codon 49 polymorphism, all were homozygous Ser49-β1AR. Subjects were infused with dobutamine (1 to 6 μg/kg/min) with or without bisoprolol (10 mg orally) pretreatment, and PRA, heart rate, contractility, and blood pressure were assessed.ResultsWith regard to PRA, dobutamine increased PRA more potently in Arg389-β1AR versus Gly389-β1AR subjects. Bisoprolol markedly suppressed the dobutamine-induced PRA increase in Arg389- but only marginally in Gly389-β1AR subjects. With regard to hemodynamics, dobutamine caused larger heart rate and contractility increases and diastolic blood pressure decreases in Arg389- versus Gly389-β1AR subjects. Bisoprolol reduced dobutamine-induced heart rate and contractility increases and diastolic blood pressure decreases more potently in Arg389- versus Gly389-β1AR subjects.ConclusionsCodon 389 β1AR polymorphism is a determinant not only of hemodynamic effects but also of PRA. Thus, β1AR polymorphisms may be useful for predicting therapeutic responses to βAR-blocker treatment.