The Arg389Gly β1-adrenoceptor polymorphism does not affect cardiac effects of exercise after parasympathetic inhibition by atropine
Authors:
- Heike BruckHBHeike Bruck
- Otto-Erich BroddeOBOtto-Erich Brodde
- 1 January 2006
- journal article
- research article
- Published by Wolters Kluwer Health in Pharmacogenetics and Genomics
- Vol. 16 (1) , 9-13
Abstract
In vitro, Arg389Gly β1-adrenoceptor (AR) polymorphism exhibits decreased β-AR signalling. In vivo, β1-AR-mediated cardiac effects of exercise showed no genotype-dependent differences in Arg389 vs. Gly389 β1-AR subjects. We studied in 16 male subjects homozygous Arg389 or Gly389 β1-AR, whether blockade of parasympathetic activity might unmask genotype-dependence of exercise effects. Subjects were infused with atropine (10 μg/kg i.v. loading dose followed by continuous i.v. infusion of 0.15 μg/kg/min throughout exercise-time); 20 min after start of atropine bicycle-exercise in supine position (25, 50, 75 and 100 W for 5 min each) was performed and heart rate, contractility, blood pressure, plasma noradrenaline and plasma-renin activity were assessed. Exercise-evoked increases in all but one parameters were not different between Arg389 and Gly389 β1-AR subjects; only plasma noradrenaline increased slightly more in Gly389 vs. Arg389 β1-AR subjects. In conclusion: It appears to be unlikely that lack of Arg389Gly β1-AR genotype-dependence of exercise-effects can be explained by influences of parasympathetic activity.Keywords
This publication has 14 references indexed in Scilit:
- The Arg389Gly ??1-adrenoceptor gene polymorphism determines contractile response to catecholaminesPharmacogenetics, 2004
- Functional responses of human ??1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphismsPharmacogenetics, 2004
- Autonomic Nervous System Pharmacogenomics: A Progress ReportPharmacological Reviews, 2004
- -Adrenoceptor polymorphismsNaunyn-Schmiedeberg's Archives of Pharmacology, 2003
- A common β1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockadeClinical Pharmacology & Therapeutics, 2003
- Polymorphisms of the β1-adrenergic receptor predict exercise capacity in heart failureAmerican Heart Journal, 2002
- Arg389Gly ??1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivoPharmacogenetics, 2001
- A Gain-of-function Polymorphism in a G-protein Coupling Domain of the Human β1-Adrenergic ReceptorJournal of Biological Chemistry, 1999
- Common polymorphisms of β1-adrenoceptor: identification and rapid screening assayThe Lancet, 1999
- Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramineNaunyn-Schmiedeberg's Archives of Pharmacology, 1997