Induction of duodenal ulcers in rats under water-immersion stress conditions. Influence of stress on gastric acid and duodenal alkaline secretion.

We investigated the influence of stress on gastric acid and duodenal HCO3- secretion in rats, and examined whether duodenal ulcers develop in rats under stress conditions in the absence or presence of acid hypersecretion caused by histamine. Either restraint alone or restraint plus water-immersion stress induced lesions in the stomach but not in the duodenum. However, subcutaneous administration of histamine dihydrochloride (40 mg/kg every 2.5 h for a total of three times) to stressed rats produced macroscopically visible damage in the proximal duodenum as well as in the stomach within 8 h of exposure to stress, and the incidence of duodenal lesions was 100% in the water-immersion group (24.8 +/- 3.8 mm2, n = 8). Histamine alone had no effect on either region. These lesions in the duodenum caused by water immersion plus histamine were prevented by subcutaneously administered cimetidine (30, 100 mg/kg) or 16,16-dimethyl prostaglandin E2 (10, 30 micrograms/kg) in a dose-related manner, but not by atropine (1, 3 mg/kg). Restraint decreased acid secretion by 40%, and additional water immersion restored the decreased acid secretion to normal levels. Basal duodenal HCO3- secretion was decreased to about 70% of normal values (5-6 microEq/15 min) in the restraint group, and after additional water immersion further declined to the values of 1.5-2 microEq/15 min. An increase of HCO3- secretion caused by acid was significantly inhibited by water immersion but not by restraint. Histamine significantly increased acid secretion but did not affect duodenal HCO3- secretion. In the rats treated with both water immersion and histamine, acid secretion was significantly reduced by either cimetidine (100 mg/kg) or 16,16-dimethyl prostaglandin E2 (30 micrograms/kg), whereas duodenal HCO3- secretion was significantly increased by 16,16-dimethyl prostaglandin E2. Atropine had little effect on either acid or HCO3- secretion. These results suggest that exposure of rats to stress decreases duodenal HCO3- secretion and increases the susceptibility of the mucosa to acid emptied from the stomach, thereby inducing duodenal ulcers if acid hypersecretion is concomitantly present.