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Human response to alpha‐2‐adrenergic agonist stimulation studied in an isolated vascular bed in vivo: Biphasic influence of dose, age, gender, and receptor genotype
Author(s) -
King D.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.023
Subject(s) - agonist , stimulation , in vivo , alpha (finance) , adrenergic receptor , alpha 2 adrenergic receptor , endocrinology , medicine , genotype , clonidine , receptor , pharmacology , adrenergic , chemistry , biology , gene , construct validity , biochemistry , microbiology and biotechnology , nursing , patient satisfaction
Background Activation of α2‐adrenergic receptors regulate a spectrum of physiologic responses, including blood pressure. Objectives This study explored local vascular responses in humans triggered by a highly selective α2‐adrenergic agonist (azepexol, B‐HT 933). Methods We evaluated dorsal hand vein responses to the infusion of azepexol, assessing venodilation, as well as maximal extent of venoconstriction, and the dose that produced a half‐maximal effect, in 50 adults. Genomic DNA was evaluated at polymorphisms of the α2B‐adrenergic receptor gene ( ADRA2B ). Results We found initial venodilation to low doses of azepexol, followed by venoconstriction to higher doses. Younger individuals venodilated less than older individuals to low doses, but venoconstricted to a greater extent at higher doses. Men had less venodilation than women to low doses, but greater venoconstriction with higher doses. Several common polymorphisms at ADRA2B (In/Del[Glu322–325], G‐98C, C1182A and C1776A) did not associate with the response. The A36G (Thr12Thr) synonymous SNP displayed a non‐significant trend (p=0.073) toward higher Kd in A/G heterozygotes compared to A/A homozgytotes. Conclusions Local infusion of a selective α2‐adrenergic agonist, azepexol, produces biphasic responses. These responses show prominent differences as a function of age and gender, but appear not to depend on common allelic variations at the ADRA2B receptor. Clinical Pharmacology & Therapeutics (2005) 77 , P5–P5; doi: 10.1016/j.clpt.2004.11.023