Published Online
on December 1, 2003

A more recent version of this article appeared on January 1, 2004

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Submitted on July 24, 2003
Revised on July 31, 2003

Alpha₂-Adrenergic Receptor-Induced Vascular Constriction in Blacks and Whites

Mordechai Muszkat; Gbenga G. Sofowora; Alastair J.J. Wood; and C. Michael Stein^*

From the Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.

^* To whom correspondence should be addressed. E-mail: michael.stein{at}vanderbilt.edu.

Abstract--Black Americans have a reduced hypotensive response to the ₂-adrenergic receptor agonist clonidine compared with whites, despite similar central sympathoinhibition. This reduced hypotensive response might be explained by greater postsynaptic vascular ₂-adrenergic receptor vasoconstrictive response. However, clonidine has a low ₂/₁ selectivity ratio. Therefore, to determine the role of altered ₂-adrenergic receptor vascular sensitivity in ethnic differences in vascular response, we compared local vascular responses with the highly selective ₂-adrenergic receptor agonist dexmedetomidine in healthy black (n=18) and white (n=19) subjects. Increasing doses of dexmedetomidine (0.001 to 1000 ng/min) were infused into a dorsal hand vein, and the local response was measured with a linear variable differential transformer. Dexmedetomidine caused pronounced venoconstriction, with an average (±SD) maximum response of 74.5±17.72% but with no difference between blacks and whites. There was substantial intersubject variability in the sensitivity to dexmedetomidine; the dose resulting in 50% (ED₅₀) of maximum vasoconstriction ranged from 0.08 ng/min to 256 ng/min. The geometric mean ED₅₀ was 2.28 ng/min (95% CI, 0.02 to 271.6 ng/min) in blacks and 1.58 ng/min (95% CI, 0.11 to 24.55 ng/min) in whites (P=0.59). Our data indicate that ₂-adrenergic receptor-induced venoconstriction is similar in blacks and whites. These findings do not support the hypothesis that altered ₂-adrenergic receptor sensitivity is the explanation for the decreased blood pressure response to systemic administration of clonidine in blacks. The response to dexmedetomidine provides a model that will allow further study of the regulation of ₂-adrenergic receptor-mediated vascular responses

Key words: adrenergic receptor agonists • ethnicity • human • receptors, adrenergic, alpha • vasoconstriction • veins

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