Effect of cimetidine on HCl-taurocholate-induced esophageal mucosal injury

The effect of the histamine H2-receptor antagonist, cimetidine, on the resistance of esophageal mucosa was investigated in an experimental model of acute esophagitis. Esophagitis was induced by perfusing an isolated segment of rabbit esophagus in situ with a solution containing HCl and taurocholate, with or without pretreatment with cimetidine (10 mg/kg and 100 mg/kg i.m.). The degree of esophageal mucosal integrity changes in transmucosal potential difference as well as mucosal permeability to H+, Na+ and two neutral molecules of different sizes, 3H-H2O and 14C-erythritol. The gross mucosal damage was also estimated. The results indicated that cimetidine in the larger dose (100 mg/kg) significantly diminished the permeability changes in esophageal mucosa induced by exposure to HCl-taurocholate, thus seeming to enhance the resistance of that mucosa against damage. In contrast, the smaller dose (10 mg/kg) did not significantly modulate the permeability changes induced by HCl-taurocholate. It is concluded that, although high doses of cimetidine seem to have a direct protective action on esophageal mucosa, the beneficial influence of therapeutic cimetidine dose given for clinical esophagitis is mainly mediated by its antisecretory action.