PERSISTENCE OF EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITORS - COMPARISONS ON BLOOD-FLOW AND PLASMA EXUDATION IN GUINEA-PIG SKIN

Plasma protein extravasation has been measured in guinea pig skin usin g I-125-albumin and blood flow using (133)Xenon (Xe-133) clearance. Th e nitric oxide (NO) synthase inhibitors N-G-nitro-L-arginine methyl es ter(L-NAME), N-G-monomethyl-L-arginine (I-NMMA) and N-G-nitro-L-argini ne (L-NOArg) and the alpha-adrenoceptor agonist, phenylephrine, inhibi ted bradykinin induced plasma protein extravasation when co-injected w ith the peptide. The inhibitory effects of L-NAME and L-NOArg lasted f or up to 8 and 4 h, respectively, whereas phenylephrine and L-NMMA had no persistent inhibitory effects. When co-injected with Xe-133, L-NAM E, L-NMMA, L-NOArg and phenylephrine, but not D-NAME, produced signifi cant reductions in skin blood flow. When injected prior to Xe-133, L-N AME and L-NOArg, but not phenylephrine or L-NMMA, significantly reduce d flow. The effect of L-NAME on flow was not significant at 8 h. Thus, although the inhibitory effects of the NO synthase inhibitors on medi ator induced plasma protein extravasation show correlations with their effects on blood flow, the persistent effect of L-NAME on exudation a ppears to extend beyond its effect on flow. (C) 1997 Elsevier Science B.V.