EFFECTS OF ENDOGENOUS AND EXOGENOUS NITRIC-OXIDE ON GASTRIC ALKALINE SECRETION IN ANESTHETIZED RATS

The influence of nitric oxide (NO) on gastric HCO3- secretion was exam ined using N-G-nitro-L-arginine methyl ester (L-NAME: NO synthase inhi bitor) and nitroprusside (NO doner) in the anesthetized rats. The rat stomach was mounted on a chamber, perfused with saline, and HCO3- secr etion was measured at pH 7.0 using a pn-stat method and by adding 10 m M HCl (acid secretion had been inhibited by pretreatment with omeprazo le). The HCO3- secretion was decreased by nitroprusside (4 mg kg(-1), i.v.) and increased by L-NAME (1-5 mg kg(-1), i.v.), respectively. The stimulatory effect of L-NAME was antagonized by co-administration of L-arginine (200 mg kg(-1), i.v.) and nitroprusside (4 mg kg(-1),i.v.), whereas the effect of nitroprusside was antagonized by the guanylate cyclase inhibitor methylene blue (10 mg kg(-1), i.v.). Nitroprusside ( 2-8 mg kg(-1), i.v.) also caused a significant decrease in the HCO3- s ecretory responses induced by not only L-NAME (10 mu g kg(-1) h(-1)) b ut also by 16,16-dimethyl prostaglandin E(2) (10 mu g kg(-1) h(-1)), a nd this effect was also significantly antagonized by prior administrat ion of methylene blue. These findings suggest that NO has an inhibitor y effect on gastric HCO3- secretion, and this effect may be mediated b y the guanylate cyclase-cyclic GMP system. The stimulation by L-NAME o f HCO3- secretion may be in part due to a removal of the inhibitory in fluence of endogenous NO on this secretion.