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 nitrop russide (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 sy nthase (NOS) inhibitor and lipopolysaccharide (LPS, 3 mg kg(-1)), a NOS ind ucer have been administered prior to pylorus ligation. The effects of these interventions on the gastric mucosal nitrite content, the incidence of ulc ers, the ulcer index, the volume of gastric secretions and the free and tot al acidity 4 h after pylorus ligation were investigated. SNP, L-Arg and LPS pretreatment increased the mucosal nitrite contents and protected the anim als against pyloric-ligation-induced increase in acidity and ulcer index. H owever, inhibition of NOS activity by L-NAME (10 mg kg(-1)) decreased the n itrite content and augmented the ulcer-induced increase in the gastric acid contents. Coadministration of L-Arg with L-NAME prevented the L-NAME-induc ed changes. Interventions which increased the mucosal nitrite content were found to be protective against ulcers. However, the NOS inhibitor L-NAME de creased mucosal nitrite levels and was ulcerogenic. Results obtained thus i ndicate the protective effect of NO on the pyloric-ligation-induced ulcers in the rat. (C) 1999 The Italian Pharmacological Society.