TOPICAL ASPIRIN PLUS HCL GASTRIC LESIONS IN THE RAT - CYTOPROTECTIVE EFFECT OF PROSTAGLANDIN, CIMETIDINE, AND PROBANTHINE

Abstract

The effect of representative agents of 3 classes of antisecretory compounds: prostaglandins, histamine H2-receptor antagonist, and anticholinergic agents, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg) plus HCl (150 mM) in the pylorus-ligated rat was studied. Acid was given exogenously so as to negate any antisecretory effect of the drugs studied. Both nonantisecretory and antisecretory doses of each agent, as determined by preliminary secretory studies, were employed. The prostaglandin analog 16,16-dimethyl prostaglandin E2, the H2-receptor antagonist cimetidine, and the anticholinergic agent probanthine, in both doses studied, all significantly reduced lesion formation. The H1-receptor antagonist mepyramine neither protected by itself nor enhanced the protective effect of cimetidine. Pepsin release into the gastric content increased with increasing mucosal damage. Addition of pepsin to the gastric instillate had no effect on severity of lesions in any group, which indicates that the increased pepsin was the result of, and not the cause of, the mucosal damage. Apparently all 3 classes of antisecretory agents studied are also cytoprotective, i.e., they can protect against gastric mucosal injury by topical aspirin plus HCl by some mechanism other than inhibition of acid and pepsin secretion.