Role of nitric oxide in the regulation of microvascular perfusion in humanskin in vivo

1. Nitric oxide (NO) concentrations were measured in dialysate from healthy human skin, in vivo, both at rest and during the inflammatory response to intradermal histamine or bradykinin. Changes in dialysate NO concentration, measured by electrochemical detection, were related to changes in dermal v ascular perfusion, measured using scanning laser Doppler imaging. 2. Basal NO concentration in dermal microdialysate was 0.60 +/- 0.14 mu M ( mean +/- S.E.M.). Following the intradermal injection of histamine, a trans ient, time-dependent increase in NO concentration was measured in areas of skin incorporating the weal and in others incorporating the flare. The incr ease in NO concentration was associated with an increase in dialysate cGMP concentration in both the weal and flare areas. 3. Addition of N-G-nitro-L-arginine-methyl ester (L-NAME, 5 mM) to the prob e perfusate resulted in an inhibition of the histamine-induced increase in NO and cGMP. Moreover, the reduction in dialysate NO concentration was asso ciated with a reduction in dermal vascular flux, both under basal condition s and within the weal and flare response. 4. These results demonstrate, by the use of microdialysis, that vasoactive mediators can be measured in healthy human skin in vivo. They provide direc t evidence that endogenous concentration of NO increases during the inflamm atory weal and flare response to histamine and that the increase in dermal NO concentration is associated with increases in cGMP concentration and der mal vascular perfusion, thus confirming a role for NO in vasoregulation in human skin.