Role of nitric oxide in omeprazole protection of the gastric mucosa in rats.

OBJECTIVE: To understand the role of nitric oxide in the protection mechanism for the gastric mucosa in rats provided by omeprazole. METHODS: Intravenous injections with omeprazole, N -nitro-L-arginine methyl ester (L-NAME), L-arginine, or D-arginine were administered in rats with gastric mucosal lesion induced by pure ethanol. Gastric mucosal blood flow (GMBF), pH of the gastric juice and gastric mucosal NO 2 /NO 3 ratio were determined and the changes of ulcer index and the severity of tissue necrosis and neutrophil infiltration observed. RESULTS: The ulcer index of rats with omeprazole treatment was much lower than that of the control group (P<0.01) with lesser degree of tissue necrosis and neutrophil infiltration (P<0.01). The protective effect of omeprazole was significantly inhibited by prior administration of L-NAME that, however, was antagonized by prior administration of L-arginine, but not D-arginine. Intravenous omeprazole administration obviously increased GMBF and gastric mucosal NO-2 /NO 3 ratio, and such effect, apart from its action against secretion, could be counteracted by pretreatment with L-NAME. CONCLUSION: Omeprazole can exert important protection against gastric mucosal lesion in rats mediated by nitric oxide, and the action of omeprazole against gastric acid secretion contributes little to the protective effect.