Microvascular basis of gastric mucosal protection

The gastric microcirculation was investigated with the in vivo microscopic analyzing system and reflectance spectrophotometry. The topical administration of either ethanol (greater than or equal to 20%), indomethacin (0.1 mg/kg), leukotriene C4 (0.1 microgram), and platelet activating factor (PAF) (125 micrograms) decreased mucosal blood flow and mucosal blood oxygenation. The subsequent reperfusion of blood and/or addition of hydrocholoride (0.2 N) induced the gastric bleeding and ulceration. Pretreatment with calcium channel blockers (verapamil, flunaridine, and diltiazem) significantly reduced the gastric lesions induced by mucosal ischemia followed by reperfusion. Lipid peroxidation increased only after reperfusion, which was also blocked by pretreatment with calcium channel blockers. Thus, the calcium ion influx and the membrane lipid peroxidation followed by mucosal hypoxia might have a role in the mucosal cell death. The results indicate that the gastric surface mucosal circulation plays an important role in the mucosal protection against high concentrations of ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), PAF, and leukotriene C4.