Effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion in pylorus-ligated rat

Abstract

The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion were evaluated in a pylorus-ligated rat model. Oral administration of salicylate (50 mg/kg), aspirin (50 mg/kg), and indomethacin (3.5 mg/kg) significantly increased ulcerogenesis over the basal value by six- to sevenfold, but ibuprofen's (10 mg/kg) fourfold increase was not significant. Aspirin in conjunction with histamine (0.5 mg/kg subcutaneously) significantly increased ulcerogenesis by 2.7-fold compared to histamine alone. Basal acid secretion was increased significantly by 156% after indomethacin, but not by other nonsteroidal antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs, except indomethacin, significantly decreased histamine-stimulated acid secretion. Nonsteroidal antiinflammatory drugs had no effect on pepsinogen secretion. Ranitidine pretreatment (25 mg/kg intraperitoneally) significantly decreased basal acid and pepsinogen secretion in all treatment groups by >85% and >40%, respectively, and ulcerations induced by salicylate, aspirin, and indomethacin were also inhibited by 90%, 60%, and 60%, respectively. The observed inhibition of prostaglandin E₂ generation by nonsteroidal antiinflammatory drugs under basal secretory conditions appeared to correlate with the extent of ulcerogenesis. Our data support the concept that acid, in addition to inhibition of prostaglandin E₂ synthesis, plays an important role in the pathogenesis of nonsteroidal antiinflammatory drug-induced gastropathy.