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J Physiol Volume 571, Number 1, 121-130, February 15, 2006 DOI: 10.1113/jphysiol.2005.098558
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Cardiovascular

Arg16Gly polymorphism of the ß2-adrenergic receptor is associated with differences in cardiovascular function at rest and during exercise in humans

Eric M. Snyder1, Kenneth C. Beck1, Niki M. Dietz2, John H. Eisenach2, Michael J. Joyner2, Stephen T. Turner1 and Bruce D. Johnson1

Departments of 1Internal Medicine
2 Anesthesiology. Mayo Clinic and Foundation, Rochester, MN, USA

In humans, subjects homozygous for arginine (ArgArg) at codon 16 of the ß2-adrenergic receptor (ß2AR) have been shown to have greater agonist-mediated desensitization than subjects homozygous for glycine (GlyGly). We sought to determine if this substitution differentially influenced cardiovascular function during short duration (9 min) low and high intensity exercise (40 and 75% of peak work). Healthy Caucasian ArgArg (n= 16), GlyGly (n= 31) and ArgGly (n= 17) subjects matched for age, sex and peak oxygen uptake were studied. There were no differences in adrenaline (ADR) at rest or with heavy exercise, but the ArgArg group had lower ADR with light exercise (P= 0.04). Resting heart rate (HR) was higher in ArgArg (P < 0.01), while cardiac output Formula , stroke volume (SV), and mean arterial pressure (MAP) were lower than the other groups Formula for ArgArg, ArgGly and GlyGly, respectively, means ±S.E.M., P < 0.01), however, no differences were observed in systemic vascular resistance (SVR). With low intensity exercise and high intensity exercise the ArgArg group continued to have a lower Formula , SV and MAP compared to the other groups (P < 0.05), with no differences observed in SVR. During recovery, the ArgArg subjects continued to have a lower MAP but there were no differences in HR, Formula , or SVR. These data suggest that subjects homozygous for Arg at codon 16 of the ß2AR have reduced Formula and MAP at rest that persist during exercise with no evidence for differential changes over the course of exercise despite large changes in catecholamines. This may suggest possible genotype-related differences in baseline receptor function or density which causes phenotypic differences at rest that are sustained during short-term exercise.

(Received 13 September 2005; accepted after revision 5 December 2005; first published online 8 December 2005)
Corresponding author E. M. Snyder: Division of Cardiovascular Diseases, Mayo Clinic and Foundation, 200 1st Street, SW, Rochester, MN 55905, USA. Email: snyder.eric{at}mayo.edu




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