Arg16/Gly beta2-adrenergic receptor polymorphism alters the cardiac output response to isometric exercise.
Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic-receptor polymorphism have 1) greater forearm beta2-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 beta2-adrenergic receptor gene on the cardiovascular response to sympathoexcitation may have important implications in the development of hypertension and heart failure.
Eisenach
John H
JH
Dept. of Anesthesiology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA. eisenach.john@mayo.edu
Barnes
Sunni A
SA
Pike
Tasha L
TL
Sokolnicki
Lynn A
LA
Masuki
Shizue
S
Dietz
Niki M
NM
Rehfeldt
Kent H
KH
Turner
Stephen T
ST
Joyner
Michael J
MJ
D000328:Adult; D001120:Arginine / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D002302:Cardiac Output / Q000235:genetics*; D015444:Exercise / Q000502:physiology*; D005260:Female; D005998:Glycine / Q000235:genetics; D018737:Hand Strength / Q000502:physiology; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013564:Sympathetic Nervous System / Q000502:physiology; D014655:Vascular Resistance / Q000235:genetics
D018343:Receptors, Adrenergic, beta-2; D001120:Arginine; D005998:Glycine; D009638:Norepinephrine