INVOLVEMENT OF NITRIC-OXIDE AND PROSTAGLANDINS IN GASTROPROTECTION INDUCED BY BACTERIAL LIPOPOLYSACCHARIDE

Background: Lipopolysaccharide (LPS) has been proposed to act as one o f the pathogens in endotoxemia-induced gastric lesions, but its action on mucosal integrity has not been fully clarified. Methods: We compar ed the effects of LPS originating from Escherichia coli and the chemic al donor of nitric oxide (NO), S-nitroso-acetylpenicillamine (SNAP), o n acute gastric lesions induced by 100% ethanol, mucosal blood flow (G BF), and mucosa generation of prostaglandin E-2 (PGE(2)) and examined the expression of constitutive NO synthase (cNOS) and inducible NO syn thase (iNOS) mRNA in the gastric mucosa of rats treated with LPS, by u sing reverse transcription polymerase chain reaction (RT-PCR). Results : LPS (0.01- 1.0 mg/kg) or SNAP (0.37-3.0 mg/kg) given intraperitoneal ly, dose-dependently prevented ethanol-induced mucosal lesions, and th ese protective effects were accompanied by a significant increase in t he GBF and excessive mucosal release of NO. Suppression of NOS activit y by N-G-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg intravenousl y) or L-N-G-(1-iminoethyl)-lysine (L-NIL) (30 mg/kg intraperitoneally) and NOS induction by treatment with dexamethasone (2 mg/kg intraperit oneally) reversed the protective and hyperemic effects of LPS, and thi s reversal by L-NAME was significantly antagonized by addition of the substrate for NOS, L-arginine, bur not D-arginine. Both LPS and SNAP i ncreased PGE(2) generation significantly, and this effect was reduced by pretreatment with L-NAME, L-NIL, or dexamethasone. Expression of cN OS was detected by RT-PCR in the intact mucosa, but intense signals fo r expression of both cNOS and iNOS were detected in the mucosa of LPS- treated rats. Conclusions: Parenteral LPS, similarly to the chemical N O donor, SNAP, protects the gastric mucosa against ethanol-induced dam age via an increase in GBF mediated by NO due to the activation of arg inine-NO system and possibly also enhanced generation of PGE(2).