Nitric oxide attenuates hydrogen peroxide-mediated injury to porcine pulmonary artery endothelial cells.
To examine the role of nitric oxide (.NO) in vascular endothelial cell injury, cultured porcine pulmonary artery endothelial cells (PAEC) were treated with H2O2 (100-500 microM) for 30 min in the presence or absence of the .NO donors (+/-)S-nitroso-N-acetylpenicillamine (SNAP) or diethylamine nitric oxide (DEANO). H2O2 caused dose-dependent PAEC cytotoxicity detected 2 h after H2O2 treatment as the release of lactate dehydrogenase. SNAP (100 microM) and DEANO (100 microM) attenuated H2O2-induced cytotoxicity if present during H2O2 treatment. In contrast, restricting treatment with .NO donors to periods before (30 min) or after (2 h) incubation with H2O2 did not prevent PAEC injury. Furthermore, the .NO synthase inhibitor NG-nitro-L-arginine methyl ester (1 mM) sensitized PAEC to H2O2-induced injury. SNAP also attenuated H2O2-induced PAEC lipid peroxidation even if restricted to periods before or after exposure to H2O2. Thus, although .NO effectively attenuated H2O2-mediated PAEC lipid peroxidation and cytotoxicity, these effects were clearly dissociated, suggesting that the antiperoxidative effects of .NO are not sufficient to account for its cytoprotective properties.
Gupta
M P
MP
Department of Medicine, Indiana University, Indianapolis, USA.
Evanoff
V
V
Hart
C M
CM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004048:Diethylamines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000293:injuries; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase; D015227:Lipid Peroxidation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011651:Pulmonary Artery; D026423:S-Nitroso-N-Acetylpenicillamine; D013552:Swine; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors
D004048:Diethylamines; D004791:Enzyme Inhibitors; D009589:Nitrogen Oxides; D019335:Nitroarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C087229:diethylamine dinitric oxide adduct; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D014366:Tryptophan Oxygenase; D010396:Penicillamine