ROLE OF NITRIC-OXIDE IN MUCOSAL BLOOD-FLOW RESPONSE AND THE HEALING OF HCL-INDUCED LESIONS IN THE RAT STOMACH

The role of nitric oxide (NO) in the gastric mucosal blood flow respon se and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induct ion of gastric lesions, and 1 h later they were fed normally. After in duction of gastric lesions, they were repeatedly administered the NO s ynthase inhibitors N-G-nitro-L-arginine methyl ester (L-NAME 5-20 mg/k g p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with reepithelialization. Repe ated administration of L-NAME but not aminoguanidine significantly del ayed the healing of gastric lesions in a dose-dependent manner. The da maged mucosa secreted less acid, but showed a marked rise in H+ permea bility, resulting in luminal acid loss accompanied by an increase of m ucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response , increased the luminal H+ loss, and totally inhibited the mucosal hyp eremic response associated with luminal acid loss in the damaged mucos a. In addition, the deleterious influences of L-NAME on the mucosal bl ood flow response and the healing of gastric lesions were significantl y antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion an d by facilitating acid disposal in the damaged mucosa. NO mediating su ch responses and participating in the healing aspect of gastric lesion s may be produced by the constitutive type of NO synthase.