title: Alpha2-adrenergic receptor-induced vascular constriction in blacks and whites.
abstract: Black Americans have a reduced hypotensive response to the alpha2-adrenergic receptor agonist clonidine compared with whites, despite similar central sympathoinhibition. This reduced hypotensive response might be explained by greater postsynaptic vascular alpha2-adrenergic receptor vasoconstrictive response. However, clonidine has a low alpha2/alpha1 selectivity ratio. Therefore, to determine the role of altered alpha2-adrenergic receptor vascular sensitivity in ethnic differences in vascular response, we compared local vascular responses with the highly selective alpha2-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 alpha2-adrenergic receptor-induced venoconstriction is similar in blacks and whites. These findings do not support the hypothesis that altered alpha2-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 alpha2-adrenergic receptor-mediated vascular responses
authors.affiliation: Division of Clinical Pharmacology, 560 RRB, Vanderbilt University School of Medicine, Nashville, Tenn 37232-6602, USA.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Muszkat
authors.forename: Gbenga G
authors.initials: GG
authors.lastname: Sofowora
authors.forename: Alastair J J
authors.initials: AJ
authors.lastname: Wood
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D044383:Black People; D020927:Dexmedetomidine / Q000494:pharmacology; D005260:Female; D006225:Hand / Q000098:blood supply; D006801:Humans; D008297:Male; D014661:Vasoconstriction / Q000187:drug effects; D014680:Veins / Q000187:drug effects / Q000502:physiology; D044465:White People; D001741:Black or African American
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D020927:Dexmedetomidine