ROLE OF EICOSANOIDS BUT NOT NITRIC-OXIDE IN THE PLATELET-ACTIVATING FACTOR-INDUCED INCREASE IN VASCULAR-PERMEABILITY IN MOUSE SKIN

We investigated the role of endogenous eicosanoids and nitric oxide (NO) in the platelet-activating factor (PAF)-induced increase in vascular permeability in mouse skin. Subcutaneous injection of PAF (45-180 pmol/site) induced a dose-related increase in vascular permeability at the injection site. The vascular permeability induced by PAF (180 pmol/site) was significantly inhibited by pretreatment with an intraperitoneal injection of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phospho (N,N,N-trimethyl) hexanolamine (PAF receptor antagonist) (5 and 25 mg/kg) and indomethacin (cyclooxygenase inhibitor) (10 mg/kg), whereas it was not affected by concurrent intravenous administration of NO synthase inhibitors N-G-nitro-L-arginine methyl ester (10 mg/kg) or methylene blue (100 mu g/kg) nor by topical injection of N-G-nitro-L-arginine methyl ester. The inhibitory effect of indomethacin was partially reversed by topical administration of prostaglandin E(2). These results suggest that PAF increases venular permeability by activating PAF receptors and that plasma extravasation is potentiated by the release of prostanoids which cause arteriolar dilatation. However, NO is not involved in the effect of PAF in mouse skin.