Persistence of effects of nitric oxide synthase inhibitors: Comparisons on blood flow and plasma exudation in guinea pig skin

Abstract

Plasma protein extravasation has been measured in guinea pig skin using 125 I -albumin and blood flow using 133 X enon ( 133 X e) clearance. The nitric oxide (NO) synthase inhibitors N G-nitro- l-arginine methyl ester ( l-NAME), N G-monomethyl- l-arginine (l -NMMA) and N G-nitro- l-arginine ( l-NOArg) and the α-adrenoceptor agonist, phenylephrine, inhibited bradykinin induced plasma protein extravasation when co-injected with the peptide. The inhibitory effects of l-NAME and l-NOArg lasted for up to 8 and 4 h, respectively, whereas phenylephrine and l-NMMA had no persistent inhibitory effects. When co-injected with 133 X e, l-NAME, l-NMMA, l-NOArg and phenylephrine, but not d-NAME, produced significant reductions in skin blood flow. When injected prior to 133 X e, l-NAME and l-NOArg, but not phenylephrine or l-NMMA, significantly reduced 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 mediator induced plasma protein extravasation show correlations with their effects on blood flow, the persistent effect of l-NAME on exudation appears to extend beyond its effect on flow.