Effect of nitric oxide modulators on pylorus-ligation-induced ulcers in the rat.

In the present investigation, the effect of nitric oxide (NO) modulators on pylorus-ligation-induced gastric ulcers in rats was studied. Sodium nitroprusside (SNP, 1 mg kg-1), a NO donor, l-arginine (l-Arg, 300 mg kg-1), the NO precursor, nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor and lipopolysaccharide (LPS, 3 mg kg-1), a NOS inducer have been administered prior to pylorus ligation. The effects of these interventions on the gastric mucosal nitrite content, the incidence of ulcers, the ulcer index, the volume of gastric secretions and the free and total acidity 4 h after pylorus ligation were investigated. SNP, l-Arg and LPS pretreatment increased the mucosal nitrite contents and protected the animals against pyloric-ligation-induced increase in acidity and ulcer index. However, inhibition of NOS activity by l-NAME (10 mg kg-1) decreased the nitrite content and augmented the ulcer-induced increase in the gastric acid contents. Coadministration of l-Arg with l-NAME prevented the l-NAME-induced changes. Interventions which increased the mucosal nitrite content were found to be protective against ulcers. However, the NOS inhibitor l-NAME decreased mucosal nitrite levels and was ulcerogenic. Results obtained thus indicate the protective effect of NO on the pyloric-ligation-induced ulcers in the rat.