DIRECT MEASUREMENT OF NITRIC-OXIDE RELEASE IN GASTRIC-MUCOSA DURING ISCHEMIA-REPERFUSION IN RATS

Nitric oxide (NO) generation in the rat gastric mucosa during ischemia -reperfusion was measured using an NO-sensitive electrode. Under pento barbital sodium anesthesia, an electrode was inserted into the submuco sa from the serous membrane side in the fundus. After steady-state bas eline recording, the celiac artery was clamped for 30 min, and then is chemia-reperfusion was achieved by removing the clamp. The clamping of the celiac artery caused a decrease in blood flow and an increase in NO level in the gastric tissue. Just after the removal of the clamp, t he NO level rapidly fell and returned to the baseline level. Administr ation of N-G-nitro-L-arginine methyl ester (an NO synthase inhibitor, 30 mg/kg ip) before ischemia significantly attenuated both the increas e in NO level during ischemia and the formation of acute gastric mucos al lesions observed after 60 min reperfusion. Administration of supero xide dismutase (a superoxide radical scavenger, 10,000 U/kg iv) at the end of ischemia inhibited both the rapid decrease in NO level during the reperfusion and the gastric mucosal erosions. Because NO and super oxide radical produce a highly reactive peroxynitrite, it can be argue d that NO has an important pathological role in acute gastric mucosal injury induced by ischemia-reperfusion. Our conclusion was strongly su pported by immunohistochemical staining of nitrotyrosine residues, an indication of peroxynitrite formation.