Evaluation of the effects of nicorandil on experimentally induced gastric ulcers.
The present study was designed to evaluate the effects of a potassium channel opener, nicorandil, and to elucidate its possible mechanism of action in aspirin plus pylorus ligation induced and ethanol-induced gastric ulcers in rats. In an attempt to ascertain the involvement of K(ATP) channels in the modulation of gastric ulcers, the effects of nicorandil alone as well as in the presence of the K(ATP) channel blocker glibenclamide were studied. Nicorandil and glibenclamide were administered orally at a dose of 2 mg/kg throughout the study. Nicorandil showed significant protection in all the selected models that was evident from a significant reduction in the ulcer index. The results of nicorandil treatment were comparable with those of cimetidine treatment in both models. Glibenclamide was found to inhibit this effect of nicorandil. Further, glibenclamide showed proulcerogenic potential in ethanol and aspirin plus pylorus ligation models. In the aspirin plus pylorus ligation model, nicorandil showed a significant reduction in total acidity, pepsin activity, and protein content and a significant rise in mucin activity. The effect of nicorandil was also studied on gastric mucosal blood flow (GMBF). The GMBF was found to be more increased in the test group than in the control group, indicating enhancement of GMBF by nicorandil. Glibenclamide reversed this effect of nicorandil as well. It is concluded from our study that nicorandil possesses antiulcer activity in the models employed in the present study. This may be attributed to the opening of K(ATP) channels, inhibition of acid secretion, enhancement of mucin activity, and improvement in GMBF.
Patel
H M
HM
Department of Pharmacology, L.M. College of Pharmacy, Navarangpura, Ahmedabad 380 009, India.
Santani
D D
DD
Goswami
S G
SG
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005905:Glyburide / Q000494:pharmacology; D008026:Ligation / Q000009:adverse effects; D008297:Male; D020108:Nicorandil / Q000494:pharmacology*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D011708:Pylorus / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D011506:Proteins; D020108:Nicorandil; D000431:Ethanol; D002927:Cimetidine; D001241:Aspirin; D005905:Glyburide