Mechanisms of gastric mucosal protection in peptic ulcer formation

Abstract

The purpose of this study is to investigate the relationship between gastric mucosal blood flow (GMBF) and hydrogen ion back diffusion (HBD) during the formation of acute gastric mucosal lesion (AGML) induced by intragastric instillation of gastric mucosal barrier breakers such as HCl and/or ethanol in rats. By increasing the concentration of HCl and/or ethanol in the test solution, the decrease in GMBF became evident 5 minutes after the instillation. This decrease was parallel with the simultaneous increase in the HBD and HCO3- secretion together with the increase in AGML in a dose-response manner. These findings indicate that promotion of HBD is in fact related to the decrease of GMBF in AGML induced by HCl and ethanol. Furthermore, to evaluate the mechanism of the cytoprotection, the effects of 16, 16-dimethyl prostaglandin E2 (16, 16-dmPGE2) on decreased GMBF and promoted HBD during impairment of the gastric mucosal barrier were assessed. In addition, the amount of acid (HCl) neutralized by HCO3- secretion, which was included in the decrease in the HBD, was determined. Administration of 16, 16-dmPGE2 markedly inhibited the formation of gastric lesions macroscopically, but had no significant effects on decreased GMBF. Though promotion of HBD was also inhibited dose-dependently, the HBD did not recover to that of the control group not treated by ethanol. HCO3- secretion was increased dose-dependently by administration of 16, 16-dmPGE2, and its maximal secretion was 10% of the decrease in the acid by HBD. These results show that cytoprotection by 16, 16-dmPGE2 is strongly related to factors other than the improvement of GMBF, such as inhibition of HBD and stimulation of HCO3- secretion.