Alpha 1A-adrenergic receptor polymorphism and vascular response.
OBJECTIVE
The alpha(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 alpha(1A) adrenergic agonist, has a large genetic component. We examined the hypothesis that a common polymorphism of alpha(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 alpha(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 alpha(1A) adrenergic receptor genotypes: Phe(50) geometric mean (95% confidence interval) was 513 ng/min (287-918 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).


CONCLUSIONS
We conclude that the Arg347Cys receptor polymorphism does not alter agonist-mediated venoconstriction in vivo.
Sofowora
Gbenga G
GG
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Dishy
Victor
V
Landau
Ruth
R
Xie
Hong-Guang
HG
Prasad
Harish C
HC
Byrne
Daniel W
DW
Smiley
Richard M
RM
Kim
Richard B
RB
Wood
Alastair J J
AJ
Stein
C Michael
CM
D058646:Adrenergic alpha-1 Receptor Agonists; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011110:Polymorphism, Genetic / Q000187:drug effects; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics*
D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine