Effects of nicorandil on experimentally induced gastric ulcers in rats: A possible role of K-ATP channels

The anti-ulcer effects of nicorandil [N-(2-hydroxyethyl)nicotinamide nitrat e ester] were examined on water-immersion plus restraint stress-induced and aspirin-induced gastric ulcers in rats, compared with those of cimetidine. Nicorandil (3 and 10 mg/kg) given orally to rats dose-dependently inhibite d the development of acid-related damage (water-immersion- and aspirin-indu ced gastric lesions) in the models. Cimetidine (50 mg/kg, p.o.) also had an ti-ulcer effects in the same models. However, in the presence of glibenclam ide (20 mg/kg, i.v.), an antagonist of K-ATP channels, nicorandil did not i nhibit the formation of gastric lesions. Nicorandil (10 mg/kg) given intrad uodenally (i.d.). Like cimetidine (50 mg/kg), significantly reduced the vol ume of the gastric content, total acidity and total acid output in the pylo rus ligation model. Glibenclamide reversed the changes caused by i.d. nicor andil. I.v. infusion of nicorandil (20 mu g/kg per min) significantly incre ased gastric mucosal blood flow, without affecting blood pressure and heart rate, but the increase in the blood flow was not observed after i.v. treat ment with glibenclamide (20 mg/kg). These results indicate that nicorandil administered orally to rats produces the anti-ulcer effect by reducing the aggressive factors and by enhancing the defensive process in the mucosa thr ough its K-ATP-channel-opening property.