GASTRIC-MUCOSAL INJURY-INDUCED BY LOCAL ISCHEMIA-REPERFUSION IN RATS - ROLE OF ENDOGENOUS ENDOTHELIN-1 AND FREE-RADICAL

We investigated the role of an endogenous vasoconstrictor peptide endo thelin-l (ET-1) and free radicals in local gastric ischemia-reperfusio n injury in rats. Local gastric ischemia was induced by clamping the l eft gastric artery for 15 min and reperfusion was done for 10-30 min i n the presence of 150 mM exogenous HCl intragastrically. Local gastric ischemia and reperfusion resulted in significant macroscopic and micr oscopic gastric mucosal damage together with elevation of gastric tiss ue ET-1 concentration. Gastric tissue ET-1 was found to increase after 15 min of ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptor antagonist, bosentan, or a combination of radical scavengers (superoxide dismutase, catalase, and deferoxami ne) both attenuated gastric mucosal injury. However, the greater prote ction observed with bosentan than with radical scavengers might reflec t a preferential role of endothelin-1 in this type of injury.