title: beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians.
abstract: Recent evidence suggests that the prodownregulatory Gly16 allele of the beta-2 adrenergic receptor (beta-2 AR) is associated with essential hypertension in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 beta-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 beta-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 beta-2 AR agonist salbutamol (0.07, 0.14, and 0.21 microgram/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 (Deltatotal peripheral resistance index -17.9+/-14.4 versus -30. 6+/-8.3%, P<0.01) despite increased sympathetic counterregulation in the Arg16/Arg16 group (Deltaheart rate +16.9+/-7.0% versus +8.6+/-7. 0%, P<0.01; Deltacardiac 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 intimately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.
authors.affiliation: Department of Internal Medicine, Krankenhaus der Barmherzigen Brüder, Teaching Hospital of the Karl Franzens University Graz (Austria).
authors.forename: G
authors.initials: G
authors.lastname: Gratze
authors.forename: J
authors.initials: J
authors.lastname: Fortin
authors.forename: R
authors.initials: R
authors.lastname: Labugger
authors.forename: A
authors.initials: A
authors.lastname: Binder
authors.forename: P
authors.initials: P
authors.lastname: Kotanko
authors.forename: B
authors.initials: B
authors.lastname: Timmermann
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
authors.forename: M R
authors.initials: MR
authors.lastname: Hoehe
authors.forename: F
authors.initials: F
authors.lastname: Skrabal
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D000483:Alleles; D001120:Arginine; D001317:Austria; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D014644:Genetic Variation; D005838:Genotype; D005998:Glycine; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013318:Stroke Volume / Q000187:drug effects; D016683:Supine Position; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D044465:White People / Q000235:genetics*
chemical_list: D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D001120:Arginine; D000420:Albuterol; D005998:Glycine