Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.
OBJECTIVE
Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes.


METHODS
We administered 1 microg/kg dexmedetomidine (an alpha-2 agonist) intravenously to 80 surgical patients in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF) and of hemodynamic variables.


RESULTS
Dexmedetomidine increased LTF (vasoconstriction), induced an initial increase in systolic blood pressure and decreased heart rate in all genotype groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion, the increase in LTF was more pronounced (P=0.014) in the DD group compared to the DI and II groups. There were no significant differences in LTF values between the groups at the end of or 5 min after dexmedetomidine infusion. There were no differences in systolic blood pressure or heart rate values between the groups during or after the dexmedetomidine infusion.


CONCLUSIONS
The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.
Talke
Pekka
P
Department of Anesthesia and Perioperative Medicine, University of California, San Francisco, California 94143-0648, USA. talkep@anesthesia.ucsf.edu
Stapelfeldt
Claudia
C
Lobo
Errol
E
Brown
Ronald
R
Scheinin
Mika
M
Snapir
Amir
A
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D014661:Vasoconstriction / Q000235:genetics*
C547771:ADRA2B protein, human; C547772:Adra2b protein, mouse; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D020927:Dexmedetomidine