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

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.