Effect of (+/-)-verapamil and hydralazine on stress- and chemically-induced gastric ulcers in rats.

The influence of (+/-)-verapamil and hydralazine on stress- and various chemically-induced gastric ulcers in rats together with their influence on various biochemical parameters which affect the development of the induced ulcers was examined. Pretreatment of rats with (+/-)-verapamil (4-16 mg kg-1 orally) significantly decreased cold-stress-induced gastric ulcers and enhanced ethanol-induced ulcers. It did not affect indomethacin- (30 mg kg-1 orally) or reserpine- (5 mg kg-1 i.p.) induced ulcers. Pretreatment of the animals with hydralazine (1-10 mg kg-1 orally) significantly enhanced ethanol-, reserpine- and cold-stress-induced ulcers. It did not affect indomethacin-induced ulcers. Pretreatment of the animals with verapamil increased gastric mucus secretion, inhibited gastric acid secretion, decreased glutathione content and enhanced gastric lipid peroxidation whereas pretreatment of the animals with hydralazine significantly decreased gastric mucus secretion. Hydralazine did not affect gastric acid secretion, glutathione or gastric lipid peroxidation. The results of this study suggest that verapamil-induced protection against stress-induced ulcer may be due to its ability to suppress gastric acid secretion and to increase gastric mucus secretion. Its enhancement of ethanol-induced ulcers may be due to its ability to increase lipid peroxidation. The hydralazine-induced enhancement of the experimentally-induced ulcers may be due to its ability to suppress gastric mucus secretion.