Gastric Mucosal Resistance and Prostanoid Levels after Cimetidine Treatment in Rats

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Abstract
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 < 0.05) reduced the mucosal concentration of prostaglandin E2 and 6-keto-prostaglandin F1α 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 < 0.01) enhanced gastric mucosal lesions induced with 0.6 N HC1 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 < 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.

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