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 i mmersion and restraint stress (WRS) was provoked once in rats with and without pretreatment of ranitidine (40 mg/kg/s.c.) and gastric adapta tion 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), w ith pretreatment with ranitidine (40 mg/kg/s.c.) and with withdrawal o f ranitidine prior to the last exposure to WRS. Luminal acidity, mean lesion number, histology and cell proliferation (PCNA-labeling index) were determuned and the expression of EGF and TGF alpha was assessed b y immunohistochemistry. Pretreatment with ranitidine increased signifi cantly luminal acidity and WRS applied once with ranitidine pretreatme nt resulted in a significant decrease of number of lesions. Gastric mu cosa adapted to repeated WRS did show a reduction in the mean lesion n umber by about 60% as compared to that induced by WRS applied once. Ab out 3 fold increase in the expression of EGF was observed in the group adapted to repeated WRS. Expression of TGF alpha was not significantl y different from that in intact rats. We conclude that gastric adaptat ion to stress leads to a decrease in gastric lesions and to an increas e in expression of EGF, Pretreatment with ranitidine that induces achl orchydria results in additional reduction in the number of stress lesi ons.