Systemically administered alpha2-agonist-induced peripheral vasoconstriction in humans.
BACKGROUND
alpha(2)-Adrenoceptors mediate both sympatholytic and vasoconstrictive hemodynamic effects. The goal of this study was to profile the peripheral vasoconstrictive effects of a selective alpha(2)-adrenoceptor agonist in isolation from the sympatholytic effects it also induces.


METHODS
The authors administered increasing plasma target concentrations of dexmedetomidine (0.075, 0.15, 0.3, and 0.6 ng/mL) or saline placebo to healthy young volunteers in whom the sympatholytic effects of the drug were attenuated in one of two ways: general anesthesia (propofol-alfentanil-nitrous oxide) or axillary brachial plexus block. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger (LTF) and hemodynamic variables. Measurements made before and during the four steps of infusion were compared by repeated-measures ANOVA.


RESULTS
In anesthetized volunteers, all concentrations of dexmedetomidine increased LTF (vasoconstriction) and systolic blood pressure (P < 0.001 for both), whereas placebo did not. In awake volunteers, all concentrations decreased systolic blood pressure (P < 0.001). Concentrations of 0.15, 0.3, and 0.6 ng/mL decreased LTF (vasodilation) in the neurally intact hand; in contrast, the same concentrations increased LTF (vasoconstriction) in the sympathectomized hand (P < 0.001 for both).


CONCLUSIONS
The results of this study are the first to characterize the lower end of the dose-response curve for vasoconstriction induced by dexmedetomidine. By denervating the vascular bed of interest or by decreasing sympathetic nervous system activity, the authors were able to observe vasoconstriction induced by a systemically administered alpha(2)-agonist with minimal interference from the sympatholytic effects of the drug.
Talke
Pekka
P
Department of Anesthesia and Perioperative Medicine, University of California, San Francisco, 94143, USA. talkep@anesthesia.ucsf.edu
Lobo
Errol
E
Brown
Ronald
R
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D000768:Anesthesia, General; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001917:Brachial Plexus; D020927:Dexmedetomidine / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005385:Fingers / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006452:Hemoglobinometry; D006801:Humans; D008297:Male; D009407:Nerve Block; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D013563:Sympathectomy, Chemical; D014661:Vasoconstriction / Q000187:drug effects*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D020927:Dexmedetomidine