β-2 Adrenergic Receptor Variants Affect Resting Blood Pressure and Agonist-Induced Vasodilation in Young Adult Caucasians

Abstract

Abstract —Recent evidence suggests that the prodownregulatory Gly16 allele of the β-2 adrenergic receptor (β-2 AR) is associated with essential hypertension in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 β-2 AR variants on hemodynamics, we investigated the agonist-mediated in vivo vasodilation in normotensive Austrian Caucasians and analyzed the results with respect to the Gly16/Arg16 polymorphism. Fifty-seven normotensive men, 20 to 32 years of age with body mass index of 18.7 to 29.9 kg/m ² , were genotyped for the Arg16/Gly16 β-2 AR alleles. All 15 Gly16/Gly16 subjects, all 12 Arg16/Arg/16 subjects, and 27 of 30 heterozygous subjects underwent hemodynamic measurements while supine after an overnight fast. The observers were unaware of the subjects’ genotypes. The subjects received a graded infusion of the selective β-2 AR agonist salbutamol (0.07, 0.14, and 0.21 μg/kg per minute, respectively), each dose over 8 minutes. Stroke volume and blood pressure were determined continuously by means of impedance cardiography and oscillometry, respectively. The last 4 minutes of each infusion were evaluated statistically. Basal mean blood pressure was higher in the Gly16/Gly16 subjects compared with Arg16/Arg16 subjects (mean±SD: 81.6±6.14 versus 75.2±4.93 mm Hg, P P P P <0.05). Our results provide additional evidence that the Gly16/Arg16 alleles of the β-2 AR are intimately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.