The interaction between endogenous nitric oxide (NO), elicited by administration of Escherichia coli lipopolysaccharide, and cyclooxygenase system, in ethanol-induced injury in rat gastric mucosa, was investigated. Administration of graded doses of lipopolysaccharide reduced the gastric mucosal injury in response to ethanol. The ex vivo production of both nitrite and prostaglandin Einf 2 was increased in dose-related manner by lipopolysaccharide. Pretreatment with dexamethasone, L-Nsup 6-(1- Iminoethyl)lysine(dihydrochloride) and L-N(G)-nitro arginine methyl ester inhibited the protection associated with lipopolysaccharide treatment and the ex vivo production of both, nitrite and prostaglandin Einf 2. The pretreatment with L-arginine counteracted the decrease of nitrite and prostaglandin Einf 2 production in lipopolysaccharide-treated rats in which nitric oxide synthesis was blocked by L-Nsup 6-(1-Iminoethyl)lysine(dihydrochloride). Administration of sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine caused a close related enhancement in the accumulation of prostaglandin Einf 2. Indomethacin administration and N-(2-Cyclohexyloxy-4-nitrophenyl)methanesulfonamide were ineffective in suppressing lipopolysaccharide-mediated protection against ethanol-induced damage, and in suppressing ex vivo increase of nitrite whereas the ex vivo increase of prostaglandin Einf 2 was prevented in a dose- related fashion. These results indicate that in ethanol-induced rat gastric injury, endogenous NO elicited by lipopolysaccharide or released by NO donors is able to activate the cyclooxygenase pathway, and the protective effect of lipopolysaccharide is dependent upon NO formation.
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