ABSTRACT
The influence of the calcium channel blockers verapamil and isradipine on gastric ulceration and glandular wall mast cell count in rats was investigated and compared with that of cimetidine [H2 antagonist]. Two different models for induction of experimental gastric ulcer were performed; cold restraint stress ulcer and indomethacin - induced gastric ulcer. Restraint at 4°C for 1 h or single bolus dose of indomethacin 30 mg/kg p.o, produced a marked gastric mucosal ulceration in saline pretreated controls. The pretreatment with single I.P injection. of either cimetidine [100 mg/ kg], verapamil [4 mg/kg] or isradipine [0.5 mg/kg] 30 minutes before cold restraint or indomethacin administration produced a significant reduction in mean gastric ulcer severity score and reduced incidence of ulceration in both macroscopic and microscopic examinations of stomachs of different groups. Both verapamil and isradipine are more or less equally effective in reducing gastric damage produced by either stress or indomethacin, however, cimetidine produced significant greater protective action. Cold restraint produced a marked decrease in mucosal mast cell count. This degranulating action of stress was prevented with verapamil or isradipine but cimetidine did not produce any significant effect. It is possible that decreased amine release [Histamine and 5 HT.] from mast cell may be responsible for the antiulcer effect of Ca channel blockers, since mast cell degranulation seems to play an important role in pathogenesis of stress gastric ulcers. Other suggested anti-ulcer mechanisms of Ca[++] channel blockers are discussed in the light of the available literature, including decreased stomach wall motility, reduced gastric acidity, peripheral and central interference with vagal overactivity, stimulation of gastric PG, synthesis and/or antioxidant action that counteract stimulation of gastric lipid peroxidation produced by stress or indomethacin. This study proved the potential value of Ca" channel blockers in the management of two different models of experimental gastric ulcers, however, a controlled clinical study is needed before any attempt to extrapolate ulcer therapy in rats to ulcer therapy in man