Neutrophils, lipid peroxidation, and nitric oxide in gastric reperfusion injury in rats.
Nitric oxide (NO) modulation of ischemia-reperfusion injury was investigated by measuring lipid peroxide and neutrophil accumulation in rat stomachs treated with NG-nitro-L-arginine (L-NNA), a specific NO synthase inhibitor. Ischemia-reperfusion injury was induced in the rat stomach. Treatment with L-NNA for 3 days at a dose of 3 mg/kg/day significantly enhanced this injury. This enhancement was reversed by the simultaneous administration of L-arginine at a dose of 30 mg/kg/day. Both thiobarbituric acid (TBA)-reactive substances, an index of lipid peroxidation, and myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, were increased in the gastric mucosa after ischemia-reperfusion. L-NNA treatment enhanced these increases in TBA-reactive substances and MPO activity. The increase in the area of gastric erosions correlated closely with accumulation of TBA-reactive substances as well as the increase in MPO activity. Enhancement of ischemia-reperfusion injury by L-NNA treatment was inhibited by injection with anti-neutrophil antibody, anti-platelet activating factor (PAF) antagonist, and anti-leukotriene B4 (LTB4) receptor antagonist. In addition, the increase in TBA-reactive substances and MPO activity was decreased by these antibodies or antagonists. Enhancement of reperfusion-induced gastric mucosal injury associated with inhibition of NO synthesis may involve neutrophil infiltration and lipid peroxide accumulation in the gastric mucosa, mediated by PAF and LTB4.
Naito
Y
Y
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Matsuyama
K
K
Yagi
N
N
Arai
M
M
Nakamura
Y
Y
Kaneko
T
T
Yoshida
N
N
Kondo
M
M
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000473:pathology; D007106:Immune Sera / Q000494:pharmacology; D007511:Ischemia; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000473:pathology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013270:Stomach / Q000098:blood supply*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004791:Enzyme Inhibitors; D007106:Immune Sera; D009566:Nitrates; D010975:Platelet Aggregation Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D007975:Leukotriene B4; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase