Importance of pepsin and stomach distension in morphological alterations of stress-induced gastric lesions in pylorus-ligated rats.

Abstract

Pylorus ligation changed the morphology and location of gastric lesions induced by water-immersion stress (WI stress) in rats; linear lesions in the corpus mucosa disappeared, and punctate lesions appeared in both the corpus and antrum, in association with the loss of H+ and the gain of Na+ in the gastric contents. Oral administration of antipeptic drugs such as amylopectin sulfate and sulfated glyptide or porcine pepsin significantly prevented or aggravated the lesions, respectively, although another type of elongated lesion appeared in response to high doses of antipeptic drugs. These antipeptic drugs or exogenous pepsin significantly reduced or increased pepsin activity, respectively, without effect on the acid output. Similar punctate lesions were produced in the atropinized rats (10 mg/kg) by instillation of acid solution (100 mM HCl plus 54 mM NaCl) with pepsin into the pylorus-ligated stomach and subjecting to WI stress. On the other hand, when the gastric contents were drained through a fistula to prevent accumulation of gastric juice in the pylorus-ligated stomach, WI stress again induced linear lesions only in the corpus mucosa. Acid hypersecretion in these rats induced by intravenous infusion of histamine, tetragastrin, or carbachol significantly aggravated the severity of lesions but did not change their morphology. These results suggest that pepsin in the presence of acid is prerequisite for development of gastric lesions in pylorus-ligated rats induced by WI stress. The morphological alterations may be accounted for by the distensions of the stomach due to accumulation of gastric juice in the lumen caused by pylorus ligation, but not due to acid hypersecretion.