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

Hypertension - Tập 33 Số 6 - Trang 1425-1430 - 1999
Gerfried Gratze1, Jürgen Fortin1, Ralf Labugger1, Alexander Binder1, Peter Kotanko1, Bernd Timmermann1, Friedrich C. Luft1, Margret R. Hoehe1, F. Skrabal1
1From the Department of Internal Medicine, Krankenhaus der Barmherzigen Brüder (G.G., J.F., R.L., A.B., P.K., F.S.), Teaching Hospital of the Karl Franzens University Graz (Austria), and Franz Vollhard Clinic at the Max Delbrück Center for Molecular Medicine (B.T., F.C.L., M.R.H.), Medical Faculty of the Charite′, Humboldt University of Berlin (Germany).

Tóm tắt

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 <0.01). Homozygous Gly16 subjects showed a significantly decreased vasodilation during the first dose of salbutamol infusion compared with Arg16/Arg16 subjects (Δtotal peripheral resistance index −17.9±14.4 versus −30.6±8.3%, P <0.01) despite increased sympathetic counterregulation in the Arg16/Arg16 group (Δheart rate +16.9±7.0% versus +8.6±7.0%, P <0.01; Δcardiac 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 β-2 AR are intimately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.

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Hypertension

Tập 33 Số 6

1425-1430

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