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-monomethyll- 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.