Abstract
We examined the changes in vascular permeability induced by inflammatory mediators in mouse skin by the Pontamine sky blue (PSB) leakage technique. Five min after i.v. administration of PSB, mediators or saline were injected (0.1 ml/site, s.c.) into the back. Sixty min later, the dye accumulated in the skin was determined colorimetrically. Plateletactivating factor (PAF, 45-180 pmol/site), 5-hydroxy-tryptamine (5-HT, 120-960 pmol/site), substance P (100-1, 000 pmol/site) and histamine (550-5, 500 pmol/site) produced dose-related increases in vascular permeability. The dose response curve induced by bradykinin (20-80 nmol/site) was bellshaped. Pretreatment with indomethacin significantly reduced the increase in vascular permeability elicited by the 5 substances tested. Coadministration of prostaglandin (PG) E2 partially reversed the inhibitory effect of indomethacin on the PAF- or histamine induced-increase in vascular permeability. Increases in vascular permeability induced by 5-HT, substance P and bradykinin were inhibited by NG-nitro-l-arginine methyl ester (L-NAME) and methylene blue, but not by D-NAME ; however, PAF-and histamine-induced increases in vascular permeability were not affected by L-NAME.These results suggest that eicosanoids may play a role in the effect of all 5 substances tested, and especially the increases in plasma extravasation induced by PAF and histamine are mediated by the production of PGE2, and that NO may play a role, at least partly, in the case of 5-HT, substance P and bradykinin.
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