Adaptation of gastric mucosa to stress. Effect of ranitidine.

Gastric mucosal adaptation to injury by repeated application of stress is a well known phenomenon. This study was designed to determine the effect of gastric acid inhibition by ranitidine on gastric adaptation to repeated exposures to stress. In this study stress 3.5 h of water immersion and restraint stress (WRS) was provoked once in rats with and without pretreatment of ranitidine (40 mg/kg/s.c.) and gastric adaptation was examined by repeated exposures to 3.5 h of WRS applied every other day for up to 8 days with pretreatment with vehicle (control), with pretreatment with ranitidine (40 mg/kg/s.c.) and with withdrawal of ranitidine prior to the last exposure to WRS. Luminal acidity, mean lesion number, histology and cell proliferation (PCNA-labeling index) were determined and the expression of EGF and TGF alpha was assessed by immunohistochemistry. Pretreatment with ranitidine increased significantly luminal acidity and WRS applied once with ranitidine pretreatment resulted in a significant decrease of number of lesions. Gastric mucosa adapted to repeated WRS did show a reduction in the mean lesion number by about 60% as compared to that induced by WRS applied once. About 3 fold increase in the expression of EGF was observed in the group adapted to repeated WRS. Expression of TGF alpha was not significantly different from that in intact rats. We conclude that gastric adaptation to stress leads to a decrease in gastric lesions and to an increase in expression of EGF. Pretreatment with ranitidine that induces achlorchydria results in additional reduction in the number of stress lesions.