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α 1A ‐adrenergic Receptor Polymorphism and Vascular Response
Author(s) -
Sofowora Gbenga G.,
Dishy Victor,
Landau Ruth,
Xie HongGuang,
Prasad Harish C.,
Byrne Daniel W.,
Smiley Richard M.,
Kim Richard B.,
Wood Alastair J. J.,
Stein C. Michael
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.02.006
Subject(s) - phenylephrine , endocrinology , agonist , medicine , receptor , adrenergic receptor , stimulation , adrenergic , adrenergic agonist , vasoconstriction , biology , chemistry , blood pressure
Objective The α 1A ‐adrenergic receptor is highly expressed in human vasculature including resistance arteries and veins, and its stimulation is primarily responsible for adrenergically mediated smooth muscle contraction. Variability in sensitivity to phenylephrine, an α 1A adrenergic agonist, has a large genetic component. We examined the hypothesis that a common polymorphism of α 1A ‐adrenergic receptor (Arg347Cys) affects in vivo response. Methods We measured vascular sensitivity to phenylephrine using the dorsal hand vein linear variable differential transformer technique and determined α 1A ‐adrenergic receptor genotype in 74 healthy, nonsmoking adults (28 Arg/Arg, 30 Arg/Cys, and 16 Cys/Cys). Results Sensitivity to phenylephrine, expressed as the dose of phenylephrine resulting in 50% venoconstriction (Phe 50 ), was not significantly different in subjects with the 3 α 1A adrenergic receptor genotypes: Phe 50 geometric mean (95% confidence interval) was 513 ng/min (287–9–8 ng/min) for Arg/Arg, 431 ng/min (274–680 ng/min) for Arg/Cys, and 471 ng/min (197–1124 ng/min) for Cys/Cys ( P = .90). Conclusion We conclude that the Arg347Cys receptor polymorphism does not alter agonist‐mediated venoconstriction in vivo. Clinical Pharmacology & Therapeutics (2004) 75 , 539–545; doi: 10.1016/j.clpt.2004.02.006