Potassium Channel Modulators and Indomethacin-Induced Gastric Ulceration in Rats

Abstract

Background: Different mechanisms have been proposed for the pathophysiology of indomethacin-induced gastric ulceration (IIGU), including changes in gastric mucosal blood flow, motility, and acidity. It seems probable that adenosine 5'-triphosphate (ATP)-dependent potassium channels (K_ATP) have a regulatory effect on the above factors. The aim of the present study was to investigate the effects of K_ATP channel modulators, diazoxide as a channel opener and glibenclamide as a KATP antagonist, on IIGU. Methods: Male rats were starved for 24 h. Groups of 10 animals were used. Diazoxide at doses of 5, 15, and 45 mg/kg and glibenclamide at doses of 2, 6, and 18 mg/kg were injected intraperitoneally 30 min before the subcutaneous injection of 30 mg/kg of indomethacin. To assess the effects of indomethacin on the gastric mucosal vascular bed, different doses of enalapril and hydralazine, two vasodilators with mechanisms of action independent of K_ATP, were also studied. Gastric mucosal ulceration was noted, and fasting blood sugar was assayed. The data were compared between the groups. Results: Indomethacin produced gastric ulceration in 100% of rats with a severity rating of 2.15/10. This was prevented by diazoxide and aggravated by glibenclamide. Diazoxide increased and glibenclamide decreased fasting blood sugar. Neither enalapril nor hydralazine showed any effect on IIGU and/or fasting blood sugar. Conclusion: K_ATP modulators may play an important role in the pathophysiology of IIGU through a peripheral action on mucosal and submucosal blood flow of the stomach, gastric motility, acidity, or an action on the vagus complex center of the brain.