The effect of varying doses of cimetidine and omeprazole, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg; 1 ml/100 g) in 0.175 M HCl or topical sodium taurocholate (40 mM; 1 ml/100 g) in 0.175 M HCl was studied in the pylorus ligated rat. Preliminary studies revealed dose dependent inhibition of acid secretion with both cimetidine and omeprazole. Intraperitoneal cimetidine 50 mg/kg and 100 mg/kg given before topical acidified aspirin reduced mucosal lesions from a control score of 23.7 +/- 3.5 (mean +/- SEM) in which 83% of stomachs contained lesions, to 6.9 +/- 2.2 and 3.5 +/- 2.1 respectively (p less than 0.05), 36% and 27% of stomachs containing lesions. A dose of 250 mg/kg failed to reduce lesion score significantly (17.8 +/- 4.9) and 64% of stomachs contained lesions. Taurocholate-induced lesion score was reduced from a control value of 32.7 +/- 4.3 in which 97% of stomachs contained lesions to 10.8 +/- 3.3 and 15.5 +/- 3.8 by cimetidine 10 mg/kg and 25 mg/kg respectively (p less than 0.05), 62% and 68% of stomachs containing lesions. Cimetidine 50 mg/kg and 100 mg/kg failed to significantly reduce mucosal damage. Intraduodenal omeprazole (1.25 to 50 mumol/kg) given before topical acidified aspirin or taurocholate failed to reduce mucosal lesions, as did intragastric omeprazole 5 mumol/kg and 50 mumol/kg given before acidified aspirin. Cimetidine showed cytoprotective properties over a specific dose range beyond which the effect was lost despite continuing suppression of acid secretion. Omeprazole exhibited no cytoprotective activity.
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