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 beta1-adrenoceptor (beta1AR) genotype-dependent. BACKGROUND: In vitro Arg389Gly-beta1AR polymorphism exhibits decreased receptor signaling. METHODS: We studied 10 male homozygous Arg389-beta1AR subjects and 8 male homozygous Gly389beta1AR subjects; to avoid influences of codon 49 polymorphism, all were homozygous Ser49-beta1AR. Subjects were infused with dobutamine (1 to 6 microg/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-beta1AR versus Gly389-beta1AR subjects. Bisoprolol markedly suppressed the dobutamine-induced PRA increase in Arg389- but only marginally in Gly389-beta1AR subjects. With regard to hemodynamics, dobutamine caused larger heart rate and contractility increases and diastolic blood pressure decreases in Arg389- versus Gly389-beta1AR subjects. Bisoprolol reduced dobutamine-induced heart rate and contractility increases and diastolic blood pressure decreases more potently in Arg389- versus Gly389-beta1AR subjects. CONCLUSIONS: Codon 389 beta1AR polymorphism is a determinant not only of hemodynamic effects but also of PRA. Thus, beta1AR polymorphisms may be useful for predicting therapeutic responses to betaAR-blocker treatment.
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 beta1-adrenoceptor (beta1AR) genotype-dependent. BACKGROUND: In vitro Arg389Gly-beta1AR polymorphism exhibits decreased receptor signaling. METHODS: We studied 10 male homozygous Arg389-beta1AR subjects and 8 male homozygous Gly389beta1AR subjects; to avoid influences of codon 49 polymorphism, all were homozygous Ser49-beta1AR. Subjects were infused with dobutamine (1 to 6 microg/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-beta1AR versus Gly389-beta1AR subjects. Bisoprolol markedly suppressed the dobutamine-induced PRA increase in Arg389- but only marginally in Gly389-beta1AR subjects. With regard to hemodynamics, dobutamine caused larger heart rate and contractility increases and diastolic blood pressure decreases in Arg389- versus Gly389-beta1AR subjects. Bisoprolol reduced dobutamine-induced heart rate and contractility increases and diastolic blood pressure decreases more potently in Arg389- versus Gly389-beta1AR subjects. CONCLUSIONS: Codon 389 beta1AR polymorphism is a determinant not only of hemodynamic effects but also of PRA. Thus, beta1AR polymorphisms may be useful for predicting therapeutic responses to betaAR-blocker treatment.
Authors: Steven M Swift; Brigitte R Gaume; Kersten M Small; Bruce J Aronow; Stephen B Liggett Journal: Physiol Genomics Date: 2008-07-29 Impact factor: 3.107