Possible involvement of non-steroidal anti-inflammatory drugs in vagal-mediated gastric acid secretion in rats.
Effects of several non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin (ASA), indomethacin (IM), flurbiprofen (FP), ibuprofen (IP), phenylbutazone (PBZ) and flufenamic acid (FA) were studied on the gastric ulceration and gastric acid secretion induced by restraint and water-immersion stress (RWIS) or various secretagogues in rats. These drugs significantly increased ulcer formation. IM (1, 3 and 10 mg/kg, s.c.) reduced gastric mucosal prostaglandin (PG) content dose-dependently. There was an appreciable correlation between this decrease in the PG content of gastric tissue and associated ulceration. The gastric acid secretion induced by the peripheral secretagogues, methacholine, gastrin and histamine, was not significantly influenced by IM pretreatment. In contrast, the gastric acid secretion induced by the vagal mediated secretagogues, insulin, 2-deoxy-D-glucose (2-D-G) and RWIS, was markedly increased by IM pretreatment. These effects were not observed in vagotomized rats. By intracerebroventricular (i.c.v.) injection of IM, no influence was observed on the gastric acid secretion and ulcer formation induced by 2-D-G or RWIS. These results suggest that acidic NSAIDs potentiate the gastric acid output induced by stimulation of vagus nerve activity, and prostaglandins (PGs) may influence gastric acid output by regulating vagus nerve activity.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D015232:Dinoprostone; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007101:Immersion; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications; D014630:Vagus Nerve / Q000503:physiopathology*
D000893:Anti-Inflammatory Agents; D007328:Insulin; D008688:Methacholine Compounds; D011458:Prostaglandins E; D006632:Histamine; D003847:Deoxyglucose; D015232:Dinoprostone; D007213:Indomethacin