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 gastric mucosal injury. We investigated the effect of ranitidine, an H2-receptor antagonist, on neutrophil activation in vitro and in rats with stress-induced 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, production of O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 were examined in human neutrophils in vitro. The 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 neutrophil elastase as well as the production of O2-, the increase in the concentrations of intracellular calcium, a second messenger of neutrophil activation, and increases in CD11b and CD18 expression, in activated neutrophils. Ranitidine did not affect the expression of E-selectin on endothelial cells in vitro. Ranitidine significantly inhibited gastric accumulation of neutrophils and gastric mucosal lipid peroxidation in rats subjected to stress. Although oral administration of acid reversed the preventive effect of pirenzepine, an anti-cholinergic drug that inhibits gastric acid secretion, it did 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 injury.
Okajima, K; Murakami, K; Liu, W; Uchiba, M
Volume / Issue
Start / End Page
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)