Gastric mucosal resistance and prostanoid levels after cimetidine treatment in rats

We studied the effects of cimetidine administered intraperitoneally to rats at a dose of 20 mg/kg twice daily for 7 days on gastric mucosal integrity and endogenous prostaglandins. Cimetidine significantly (p less than 0.05) reduced the mucosal concentration of prostaglandin E2 and 6-keto-prostaglandin F1 alpha both 30 min and 24 h after the last injection of this drug, and the level had returned to normal 5 days later. Cimetidine significantly (p less than 0.01) enhanced gastric mucosal lesions induced with 0.6 N HCl 24 h after the last injection; this increased vulnerability had disappeared 5 days later. Cimetidine did not affect the synthesis of these prostanoids in isolated gastric mucosa in vitro. Gastric secretion, which was significantly (p less than 0.05) inhibited 30 min after the last injection of cimetidine, returned to control level 24 h after the last injection. The increase in gastric mucosal vulnerability observed 24 h after the last cimetidine injection might be related to a decrease in the prostanoid content and recovery of acid secretion.