Anti-ulcer activity of cromakalim (BRL 34915), a potassium-channel opener, against experimentally induced gastric and duodenal ulcers in rats and guinea-pigs

The effect of cromakalim, a potassium-channel opener, was studied on pylorus ligation-induced, aspirin-induced and water-immersion plus restraint stress-induced gastric ulcers in rats and on histamine-induced duodenal ulcer in guinea-pigs. Pretreatment with cromakalim (50-500 mu g kg(-1), p.o.) resulted in a significant reduction in the incidence of gastric and duodenal ulceration in each model. The anti-ulcer activity of cromakalim was comparable with that of cimetidine. Cromakalim at 100, 250 and 500 mu g kg(-1) caused a reduction in the volume of the gastric content in pylorus-ligated rats, and a dose of 250 mu g kg(-1) resulted in a significant reduction in total acidity (28.81 +/- 11.73 mEqL(-1), P < 0.02) in the pylorus ligation model. A significant reduction in total acid output was observed at doses of 250 mu g kg(-1) (84.27 +/- 22.33 mEqH(+), P < 0.02) and 500 mu g kg(-1) (120.17 +/- 24.49 mEq H+, P < 0.01) in pylorus-ligated rats. A significant reduction in the ulcer index in pylorus-ligated rats was observed at all cromakalim doses: 50 mu g kg(-1) (0.23 +/- 0.09, P < 0.05), 100 mu g kg(-1) (0.15 +/- 0.09, P < 0.02), 250 mu g kg(-1) (0.12 +/- 0.05, P < 0.01) and 500 mu g kg(-1) (0.14 +/- 0.03, P < 0.02). A significant reduction in the ulcer index of aspirin-treated rats was also observed at all cromakalim dose levels: 50 mu g kg(-1) (0.39 +/- 0.03, P < 0.01), 100 mu g kg(-1) (0.28 +/- 0.06, P < 0.01), 250 mu g kg(-1) (0.22 +/- 0.04, P < 0.001) and 500 mu g kg(-1) (0.28 +/- 0.03, P < 0.01). In the water-immersion plus restraint stress-induced gastric ulcer model, cromakalim significantly reduced gastric ulceration at all the dose levels: 50 mu g kg(-1) (28.2 +/- 2.12, P < 0.001), 100 mu g kg(-1) (20.24 +/- 1.71, P < 0.01), 250 mu g kg(-1) (19.95 +/- 1.46, P < 0.001) and 500 mu g kg(-1) (21.61 +/- 3.00, P < 0.001) but there was no consistent reduction of gastric bleeding. In addition to gastric ulcers, duodenal lesions were also reduced by pretreatment with cromakalim at all dose levels: 50 mu g kg(-1) (97.87 +/- 20.03 mm(2), P < 0.02), 100 mu g kg(-1) (70.72 +/- 12.82 mm(2), P < 0.02), 250 mu g kg(-1) (48.32 +/- 8.42 mm(2), P < 0.01) and 500 mu g kg(-1) (55.50 +/- 12.50 mm(2), P < 0.01). Cromakalim at a dose of 100 mu g kg(-1) also reduced total acidity (99.36 +/- 9.12 mEqL(-1), P < 0.02) and total acid output (172.22 +/- 45.33 mEq of H+, P < 0.05) in this model. These findings demonstrate the anti-ulcer activity of cromakalim in different experimental models and suggest its potential use in ulcer therapy.