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 NG-nitro-L-arginine methyl ester (10 mg/kg) or methylene blue (100 micrograms/kg) nor by topical injection of NG-nitro-L-arginine methyl ester. The inhibitory effect of indomethacin was partially reversed by topical administration of prostaglandin E2. 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.
Fujii
E
E
Department of Pharmacology, Tokyo Women's Medical College, Japan.
Irie
K
K
Uchida
Y
Y
Ohba
K
K
Muraki
T
T
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D015777:Eicosanoids / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D010972:Platelet Activating Factor; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin