Effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion in pylorus-ligated rat.
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. Non-steroidal 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.
Wagner
K A
KA
Department of Medicine, State University of New York Health Science Center, Syracuse 13210.
Nandi
J
J
King
R L
RL
Levine
R A
RA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity; D015232:Dinoprostone / Q000096:biosynthesis; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D007052:Ibuprofen / Q000633:toxicity; D007213:Indomethacin / Q000633:toxicity; D008026:Ligation; D008297:Male; D010435:Pepsinogens / Q000378:metabolism; D011708:Pylorus; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000097:blood / Q000633:toxicity; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010435:Pepsinogens; D012459:Salicylates; D006632:Histamine; D011899:Ranitidine; D015232:Dinoprostone; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin