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: G Gratze, J Fortin, R Labugger, A Binder, P Kotanko, B Timmermann, F C Luft, M R Hoehe, F Skrabal
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 33 Issue 6 Pg. 1425-30 (Jun 1999) ISSN: 0194-911X [Print] United States
• PMID: 10373227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Agonists
• Receptors, Adrenergic, beta-2
• Arginine
• Albuterol
• Glycine

Topics

• Adrenergic beta-Agonists (administration & dosage, pharmacology)
• Adult
• Albuterol (administration & dosage, pharmacology)
• Alleles
• Arginine
• Austria
• Blood Pressure (drug effects)
• Body Mass Index
• Genetic Variation
• Genotype
• Glycine
• Hemodynamics (drug effects, physiology)
• Heterozygote
• Humans
• Infusions, Intravenous
• Male
• Polymorphism, Genetic
• Receptors, Adrenergic, beta-2 (genetics)
• Stroke Volume (drug effects)
• Supine Position
• Vasodilation (drug effects, genetics, physiology)
• White People (genetics)