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

Abstract

Black Americans have a reduced hypotensive response to the α 2-adrenergic receptor agonist clonidine compared with whites, despite similar central sympathoinhibition. This reduced hypotensive response might be explained by greater postsynaptic vascular α 2-adrenergic receptor vasoconstrictive response. However, clonidine has a low α2/α1 selectivity ratio. Therefore, to determine the role of altered α2-adrenergic receptor vascular sensitivity in ethnic differences in vascular response, we compared local vascular responses with the highly selective α 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 α2-adrenergic receptor-induced venoconstriction is similar in blacks and whites. These findings do not support the hypothesis that altered α2-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 α 2-adrenergic receptor-mediated vascular responses.