Clonidine induces nitric oxide- and prostaglandin-mediated vasodilation in healthy human skin.
Sustained sympathetic activation not only leads to vasoconstriction but also might induce paradox vasodilation. This study was performed to explore whether and how alpha(2)-receptor stimulation mediates this vasodilation. We investigated 11 healthy subjects in 33 dermal microdialysis (MD) sessions. After nerve trunk blockade, MD fibers were inserted and perfused with physiological saline until skin trauma-related vasodilation subsided. Thereafter, fibers were perfused with either clonidine solutions (10(-3), 5 x 10(-4), 10(-4) mol/l), N(G)-monomethyl-l-arginine (L-NMMA; nitric oxide synthase blocker), acetylsalicylic acid (ASA; cyclooxygenase blocker), or combinations of these. Laser-Doppler scanning of the investigated skin revealed that clonidine not only induces vasoconstriction but subsequently also vasodilation with higher concentrations (P < 0.001). In contrast, both L-NMMA and ASA induced vasoconstriction (P < 0.001). By coapplication of 10(-3) mol/l clonidine with L-NMMA or ASA, vasodilation was partially prevented (P < 0.001). Our results demonstrate that sustained alpha(2)-receptor stimulation induces vasodilation in a dose-dependent way, which is mediated by nitric oxide and prostaglandin mechanisms in human skin.
Hermann
Daniel
D
Department of Neurology, University of Mainz, Germany.
Schlereth
Tanja
T
Vogt
Thomas
T
Birklein
Frank
F
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D012016:Reference Values; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D011453:Prostaglandins; D009569:Nitric Oxide; D003000:Clonidine