Role of luminal H+ in the pathogenesis of experimental esophagitis

mg/ml) with and without acid (HCl, 10 to 750 mM). The seuerity of mucosal damage was assessed using as indicators of mucosal integrity transmucosal potential di’erence, net j?ux of Na+, and mucosal permeability to two neutral molecules of different sizes-3H-H,0 and “C-erythritol. The data indicate that although the presence of luminal acid is needed for mucosal damage to develop, there is no relationship between the severity of the damage and the magnitude of the lumen-to-mucosa difision of Hi. Even markedly increased diffusion of H+ alone, induced by an unphysiologically high concentration of luminal acid (300 mM HCl), had only a minor influence on mucosal integrity, whereas all three test agents were able to cause severe mucosal damage in association with much lower rates of H+ diflusion. Furthermore, the severity of the mucosal damage caused by an indiuidual test agent was not dependent on the HCl concentration used (and hence on the magnitude of lumen-to-mucosa diflusion of H’) The data suggest that esophageal mucosal damage caused by taurocholate, pepsin, or lysolecithin in the presence of luminal acid is due to the direct action of the agent itself rather than to excessive accumulation of luminal H+ into the mucosal tissue.