EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITOR N-G-NITIO-L-ARGININE METHYL-ESTER ON DUODENAL ALKALINE SECRETORY AND ULCEROGENIC RESPONSES INDUCED BY MEPIRIZOLE IN RATS

The inhibition of nitric oxide (NO) production by NO synthase inhibito rs stimulates HCO3- secretion in the rat duodenal mucosa. Therefore, w e examined the effects of N-G-nitro-L-arginine methyl ester (L-NAME, t he NO synthase inhibitor) and nitroprusside (the exogenous NO donor) o n the dubdenal HCO3- and ulcerogenic responses in anesthetized rats. A nimals were administered mepirizole (200 mg/kg, subcutaneously) for in duction of duodenal ulcers, and gastric acid and duodenal HCO3- secret ions were measured with or without pretreatment with L-NAME (5 mg/kg, intravenously) or nitroprusside (4 mg/kg, intravenously). Mepirizole i ncreased acid secretion, decreased the acid-induced duodenal HCO3- sec retion, and induced hemorrhagic lesions in the proximal duodenum. The inhibition of NO production by L-NAME potentiated the acid secretory r esponse, increased the duodenal HCO3- secretion, and prevented the duo denal lesions, and these changes were all antagonized by simultaneous administration, of L-arginine (200 mg/kg, intravenously) but not D-arg inine. On the other hand, nitroprusside slightly reduced the acid resp onse but further decreased the HCO3- output, resulting in aggravation of duodenal lesions induced by mepirizole. These data suggest that the inhibition of endogenous NO production by the NO synthase inhibitor L -NAME increases duodenal HCO3- secretion and protects the duodenal muc osa against acid injury.