Inhibition of neutrophil activation by ranitidine contributes to prevent stress-induced gastric mucosal injury in rats

Objective: Activated neutrophils play a critical role in stress-induced gas tric mucosal injury. We investigated the effect of ranitidine, an H-2-recep tor antagonist, on neutrophil activation in vitro and in rats with stress-i nduced gastric mucosal injury. Design: Prospective, randomized, blinded, controlled study. Setting: Research laboratory at a university medical center. Interventions: Effects of ranitidine on neutrophil elastase release, produc tion of O-2(-), intracellular calcium concentration and expression of adhes ion molecules CD11b and CD18 were examined in human neutrophils in vitro Th e effect of ranitidine (30 mg/kg iv) on the development of gastric mucosal injury, neutrophil accumulation, and lipid peroxidation was investigated in male Wistar rats subjected to water-immersion restraint stress. Measurements and Main Results:Ranitidine inhibited the release of neutrophi l elastase as well as the production of O-2(-), the increase in the concent rations of intracellular calcium, a second messenger of neutrophil activati on, and increases in CD11b and CD18 expression, in activated neutrophils. R anitidine did not affect the expression of E-selectin on endothelial cells in vitro. Ranitidine significantly inhibited gastric accumulation of neutro phils and gastric mucosal lipid peroxidation in rats subjected to stress. A lthough oral administration of acid reversed the preventive effect of piren zepine, an anti-cholinergic drug that inhibits gastric acid secretion, it d id not affect the preventive effect of ranitidine. Leukocytopenia produced effects similar to those of ranitidine in animals subjected to stress. Conclusions: Inhibition of neutrophil activation and gastric acid secretion by ranitidine might contribute to reduce stress-induced gastric mucosal in jury.