EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON ULCEROGENESIS AND GASTRIC-SECRETION IN PYLORUS-LIGATED RAT

The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis an d gastric secretion were evaluated in a pylorus-ligated rat model. Ora l administration of salicylate (50 mg/kg), aspirin (50 mg/kg), and ind omethacin (3.5 mg/kg) significantly increased ulcerogenesis over the b asal value by six- to sevenfold, but ibuprofen's (10 mg/kg) fourfold i ncrease was not significant. Aspirin in conjunction with histamine (0. 5 mg/kg subcutaneously) significantly increased ulcerogenesis by 2.7-f old compared to histamine alone. Basal acid secretion was increased si gnificantly by 156% after indomethacin, but not by other nonsteroidal antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs, except indomethacin, significantly decreased histamine-stimula ted acid secretion. Nonsteroidal antiinflammatory drugs had no effect on pepsinogen secretion. Ranitidine pretreatment (25 mg/kg intraperito neally) 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 b y 90%, 60%, and 60%, respectively. The observed inhibition of prostagl andin E(2) generation by nonsteroidal antiinflammatory drugs under bas al secretory conditions appeared to correlate with the extent of ulcer ogenesis. Our data support the concept that acid, in addition to inhib ition of prostaglandin E(2) synthesis, plays an important role in the pathogenesis of nonsteroidal antiinflammatory drug-induced gastropathy .