Multiple nitric oxide sources in neurogenic plasma extravasation in rat hindpaw skin

The contribution of nitric oxide (NO) to capsaicin-evoked plasma extravasation was studied in rat hindpaw skin. Two inhibitors of NO synthase were used: 7-nitroindazole, with a selectivity for nerve-derived NO, and the L-arginine derivative, N(omega)-nitro-L-arginine (L-NOARG), which is a non-selective inhibitor. Plasma extravasation was induced by intraplantar injection of 5 microg/50 microl capsaicin and measured by the Evans blue leakage technique. Both acute and chronic administration of 7-nitroindazole significantly reduced capsaicin-evoked plasma extravasation in rat hind-paw skin, whereas L-NOARG enhanced it. This enhancement was abolished non-stereospecifically by either L- or D-arginine. Our results suggest that NO production from different sources yields a complex action in maintaining the endothelial integrity in neurogenic plasma extravasation.