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 pentobarbital sodium anesthesia, an electrode was inserted into the submucosa from the serous membrane side in the fundus. After steady-state baseline recording, the celiac artery was clamped for 30 min, and then ischemia-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, the NO level rapidly fell and returned to the baseline level. Administration of NG-nitro-L-arginine methyl ester (an NO synthase inhibitor, 30 mg/kg i.p.) before ischemia significantly attenuated both the increase in NO level during ischemia and the formation of acute gastric mucosal lesions observed after 60 min reperfusion. Administration of superoxide dismutase (a superoxide radical scavenger, 10,000 U/kg i.v.) at the end of ischemia inhibited both the rapid decrease in NO level during the reperfusion and the gastric mucosal erosions. Because NO and superoxide radical produce a highly reactive peroxynitrite, it can be argued that NO has an important pathological role in acute gastric mucosal injury induced by ischemia-reperfusion. Our conclusion was strongly supported by immunohistochemical staining of nitrotyrosine residues, an indication of peroxynitrite formation.
Wada
K
K
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Kamisaki
Y
Y
Ohkura
T
T
Kanda
G
G
Nakamoto
K
K
Kishimoto
Y
Y
Ashida
K
K
Itoh
T
T
D000818:Animals; D004566:Electrodes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D015424:Reperfusion; D026423:S-Nitroso-N-Acetylpenicillamine; D013270:Stomach / Q000098:blood supply*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides
D004791:Enzyme Inhibitors; D009566:Nitrates; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester