INHIBITORS OF NITRIC-OXIDE SYNTHASE IN HUMAN SKIN

The aim of this study was to investigate in human skin in vivo the rol e of nitric oxide in maintaining resting vascular tone, in the vasodil atation caused by local warming and by ultraviolet B light exposure, a nd in the response to exogenous calcitonin gene-related peptide (CGRP) , Cutaneous blood flow was assessed by planimetry of the visible eryth ema or pallor and by laser Doppler flowmetry. Intradermal injection of the inhibitor of nitric oxide synthase, N-G-nitro-L-arginine methyl e ster (L-NAME; 25 nmol), into forearm skin produced a visible pallor an d a reduction of blood flow at a controlled ambient temperature of 21 degrees C. The control, N-G-nitro-D-arginine methyl ester (D-NAME; 25 nmol) or N-G-monomethyl-L-arginine (L-NMMA; 25 nmol) did not cause pal lor or reduce blood how, L-NAME and L-NMMA caused dose- and time-depen dent increases in pallor, and reductions in cutaneous blood flow in sk in that had been locally warmed by immersion in water at 45 degrees C and in skin that had been exposed to ultraviolet B light, D-NAME and D -NMMA at comparable concentrations did not have the effects on skin bl ood how observed with the L forms, L-NAME and L-NMMA both inhibited th e increased blood flow in human skin caused by the intradermal injecti on of CGRP (12.5 or 25 pmol), The reduction of CGRP-induced increase o f blood how by L-NAME was reversed by L-arginine, Neither D-NAME nor D -NMMA inhibited the increase in blood flow caused by CGRP, Neither L-N AME nor L-NMMA inhibited the increase in blood flow in human skin caus ed by the intradermal injection of prostaglandin E(2) (63 pmol), The d ata show that nitric oxide is involved in the maintenance of resting b lood flow in human skin and also in the cutaneous vasodilator response s to local warming, ultraviolet B irradiation, or injection of CGRP.