α1A‐adrenergic Receptor Polymorphism and Vascular Response

Objective The α1A‐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 α1A adrenergic agonist, has a large genetic component. We examined the hypothesis that a common polymorphism of α1A‐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 α1A‐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 (Phe50), was not significantly different in subjects with the 3 α1A adrenergic receptor genotypes: Phe50 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