beta-2 adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians

Recent evidence suggests that the prodownregulatory Gly16 allele of the bet a-2 adrenergic receptor (beta-2 AR) is associated with essential hypertensi on in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 beta-2 AR variants on hemodynamics, we investi gated the agonist-mediated in vivo vasodilation in normotensive Austrian Ca ucasians and analyzed the results with respect to the Gly16/Arg16 polymorph ism. Fifty-seven normotensive men, 20 to 32 years of age with body mass ind ex of 18.7 to 29.9 kg/m(2), were genotyped for the Arg16/Gly16 beta-2 AR al leles. All 15 Gly16/Gly16 subjects, all 12 Arg16/Arg/16 subjects, and 27 of 30 heterozygous subjects underwent hemodynamic measurements while supine a fter an overnight fast. The observers were unaware of the subjects' genotyp es. The subjects received a graded infusion of the selective beta-2 AR agon ist salbutamol (0.07, 0.14, and 0.21 mu g/kg per minute, respectively), eac h dose over 8 minutes. Stroke volume and blood pressure were determined con tinuously by means of impedance cardiography and oscillometry, respectively . The last 4 minutes of each infusion were evaluated statistically. Basal m ean blood pressure was higher in the Gly16/Gly16 subjects compared with Arg 16/Arg16 subjects (mean+/-SD: 81.6+/-6.14 versus 75.2+/-4.93 mmHg, P<0.01). Homozygous Gly16 subjects showed a significantly decreased vasodilation du ring the first dose of salbutamol infusion compared with Arg16/Arg16 subjec ts (Delta total peripheral resistance index -17.9+/-14.4 versus -30.6+/-8.% , P<0.01) despite increased sympathetic counterregulation in the Arg16/Arg1 6 group (Delta heart rate +16.9+/-7.0% versus +8.6+/-7.0%, P<0.01; Delta ca rdiac index +39.5+/-18.5% versus 21.4+/-18.8%, P<0.05). Our results provide additional evidence that the Gly16/Arg16 alleles of the beta-2 AR are inti mately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.