Relative roles of acid and mucosal compression in ulcerogenesis in indomethacin-insulin-treated rat.
We have proposed that gastric peristaltic activity is primarily responsible for ulcerogenesis in the phenylbutazone-treated rat and that acid plays only a synergistic role. This study examines the effect of graded doses of the H2 blocker cimetidine on acid secretion and ulcerogenesis occurring during insulin-induced peristalsis in the indomethacin (Indo) -pretreated rat. The second part of the study utilizes graded gastric distension with exogenous acid to examine the role of the forceful apposition of the mucosal folds during peristalsis in lesion genesis. It is demonstrated that the inhibition of acid secretion by cimetidine reduces but does not prevent ulceration. Gastric inflation with acid obliterates mucosal folding, prevents mucosal apposition during peristalsis, and abolishes ulcerogenesis. It is concluded that mucosal compression is the primary cause of the linear lesions along the base of the mucosal folds but that acid is necessary to extend the lesions once initiated.
D000818:Animals; D002927:Cimetidine / Q000627:therapeutic use; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000209:etiology* / Q000517:prevention & control
D007328:Insulin; D002927:Cimetidine; D007213:Indomethacin