(Hypertension. 1999;33:1425-1430.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
ß-2 Adrenergic Receptor Variants Affect Resting Blood Pressure and Agonist-Induced Vasodilation in Young Adult Caucasians
From 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).
Correspondence to Falko Skrabal, MD, Prof, Krankenhaus der Barmherzigen Brüder, Teaching Hospital of the Karl Franzens University Graz, Marschallgasse 12, 8020 Graz, Austria. E-mail falko.skrabal{at}kfunigraz.ac.at
Abstract—Recent evidence
suggests that the prodownregulatory Gly16 allele of the ß-2
adrenergic receptor (ß-2 AR) is associated with essential
hypertension in African Caribbeans. To further investigate the effect
of the glycine (Gly)16 and arginine (Arg)16 ß-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/m2, were
genotyped for the Arg16/Gly16 ß-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 ß-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 (
total
peripheral resistance index -17.9±14.4 versus
-30.6±8.3%, P<0.01) despite increased sympathetic
counterregulation in the Arg16/Arg16 group (heart rate +16.9±7.0%
versus +8.6±7.0%, P<0.01; cardiac 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
ß-2 AR are intimately related to blood pressure regulation and
deserve further studies in the pathogenesis of essential
hypertension.
Key Words: hypertension, essential • molecular genetics • ß-2 adrenergic receptor • Arg16/Gly16 allele • vasodilation • impedance cardiography
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