The alpha2C-adrenoceptor deletion322-325 variant and cold-induced vasoconstriction.
OBJECTIVE
Cold-induced vasoconstriction is mediated in part by selective enhancement of local alpha(2C)-adrenoceptor (alpha(2C)-AR) activity. A common insertion-deletion variant in the alpha(2C)-AR gene (ADRA2C del322-325) results in an approximately 85% reduction of agonist-mediated function in vitro. We tested the hypothesis that individuals with the ADRA2C del322-325 variant have attenuated vasoconstriction in response to cold.


METHODS
Cutaneous digital blood flow (flux) was measured by laser Doppler flowmetry in a controlled environment at room temperature and during two cycles of graduated local heat and cold exposure in 31 subjects. Temperature-response curves were analyzed to estimate the following measures: E(min) (minimal flux during cooling), and ET(50) and ET(90) (the local temperature at which flux decreased by 50 and 90%, respectively).


RESULTS
We found no significant genotypic differences in E(min) (24.3 +/- 19.5, 30.0 +/- 20.5, and 21.5 +/- 25.9 AU for ins/ins, ins/del, and del/del genotypes, respectively; P = 0.48), ET(50) (25.5 +/- 6.0, 25.1 +/- 6.7, and 25.1 +/- 7.1 degrees C; P = 0.99), or ET(90) (20.5 +/- 4.7, 22.1 +/- 4.0, and 20.8 +/- 6.7 degrees C; P = 0.77) in either the first or second heating and cooling cycle (cycle 1 values presented).


CONCLUSIONS
The ADRA2C del322-325 variant did not affect vascular sensitivity to local cold exposure.
Friedman
Eitan A
EA
Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, 542 RRB, Nashville, TN 37232-6602, USA.
Harris
Paul A
PA
Wood
Alastair J J
AJ
Stein
C Michael
CM
Kurnik
Daniel
D
D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology*; D003080:Cold Temperature; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D012867:Skin / Q000098:blood supply; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*
C547774:ADRA2C protein, human; D018341:Receptors, Adrenergic, alpha-2