Arg16/Gly β2-adrenergic receptor polymorphism alters the cardiac output response to isometric exercise

John H. Eisenach, Sunni A. Barnes, Tasha L. Pike, Lynn A. Sokolnicki, Shizue Masuki, Niki M. Dietz, Kent H. Rehfeldt, Stephen T. Turner, Michael J. Joyner

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Abstract

Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly β2-adrenergic-receptor polymorphism have 1) greater forearm β2-receptor mediated vasodilation and 2) a higher heart rate (HR) response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the higher HR response in Gly16 subjects serves to maintain the pressor response [increased cardiac output (CO)] in the setting of augmented peripheral vasodilation to endogenous catecholamines, we measured continuous HR (ECG), arterial pressure (Finapres), and CO (transthoracic echocardiography) during isometric, 40% submaximal handgrip to fatigue in healthy subjects homozygous for Gly (n = 30; mean age ± SE: 30 ± 1.2, 13 women) and Arg (n = 17, age 30 ± 1.6, 11 women). Resting data were similar between groups. Handgrip produced similar increases in arterial pressure and venous norepinephrine and epinephrine concentrations; however, HR increased more in the Gly group (60.1 ± 4.3% increase from baseline vs. 45.5 ± 3.9%, P = 0.03), and this caused CO to be higher (Gly: 7.6 ± 0.3 l/m vs. Arg: 6.5 ± 0.3 l/m, P = 0.03), whereas the decrease in systemic vascular resistance in the Gly group did not reach significance (P = 0.09). We conclude that Gly16 homozygotes generate a higher CO to maintain the pressor response to handgrip. The influence of polymorphic variants in the β2- adrenergic receptor gene on the cardiovascular response to sympathoexcitation may have important implications in the development of hypertension and heart failure.

Original languageEnglish (US)
Pages (from-to)1776-1781
Number of pages6
JournalJournal of applied physiology
Volume99
Issue number5
DOIs
StatePublished - Nov 1 2005

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Keywords

  • Genomics
  • Hypertension
  • Sympathetic nervous system
  • β-adrenergic receptors

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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