The Arg389Gly beta1-adrenoceptor polymorphism and catecholamine effects on plasma-renin activity.
OBJECTIVE
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.
Bruck
Heike
H
Department of Nephrology, University of Essen Medical School, Essen, Germany.
Leineweber
Kirsten
K
Temme
Thomas
T
Weber
Melanie
M
Heusch
Gerd
G
Philipp
Thomas
T
Brodde
Otto-Erich
OE
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000235:genetics; D017298:Bisoprolol / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D012083:Renin / Q000097:blood*; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D004280:Dobutamine; D001120:Arginine; D012083:Renin; D005998:Glycine; D017298:Bisoprolol