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β 2 ‐Adrenergic receptor polymorphism and nitric oxide‐dependent forearm blood flow responses to isoproterenol in humans
Author(s) -
Garovic Vesna D.,
Joyner Michael J.,
Dietz Niki M.,
Boerwinkle Eric,
Turner Stephen T.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.031138
Subject(s) - medicine , endocrinology , nitric oxide , brachial artery , vasodilation , agonist , blood flow , hemodynamics , blood pressure , reactive hyperemia , receptor , forearm , pathology
Polymorphisms in the gene encoding the β 2 ‐adrenoceptor have been associated with interindividual differences in blood pressure and the diagnosis of hypertension. A common polymorphism resulting in a change from arginine to glycine at amino acid 16 (Arg16 → Gly) enhances agonist‐promoted downregulation of receptor expression in vitro . It is unknown whether genotype‐dependent differences in nitric oxide generation contribute to differences in vasodilator responses to β 2 ‐agonists in vivo . To address this question, venous occlusion plethysmography was used to measure forearm blood flow responses to graded brachial artery infusions of the β‐agonist isoproterenol in 41 healthy normotensive Caucasian adults (mean age (± s.d .) = 29 ± 6 years), who were either Arg16 ( n = 18) or Gly16 ( n = 23) homozygotes. Compared to Arg16 homozygotes, Gly16 homozygotes demonstrated significantly greater blood flow responses to isoproterenol ( P = 0.02). After inhibition of nitric oxide synthase by N γ ‐monomethyl‐ l ‐arginine, blood flow responses did not differ significantly between genotype groups ( P = 0.27). Consequently, effects of the Arg16 → Gly polymorphism on forearm blood flow responses to isoproterenol appear to be dependent on differences in endothelial generation of nitric oxide. In contrast to previous reports based on systemic infusions of β 2 ‐agonists, our findings indicate that regional blood flow responses to locally infused isoproterenol are significantly greater in Gly16 than in Arg16 homozygotes.