Endothelial damage induced by nitric oxide: synergism with reactive oxygen species.
Interactions of reactive oxygen and nitrogen species to mediate endothelial cell damage were studied in vitro. S-Nitroso-N-acetyl-DL-penicillamine (SNAP), 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) and sodiumnitroprusside (SNP) were used as NO.-donating agents. The toxicity of SIN-1 (5 mM), which produces both O2-. and NO., was reduced when catalase was added to remove H2O2 whereas superoxide dismutase had a marginal protective influence. Low doses of H2O2 producing enzymes added to low doses of SNAP (1 mM) or SNP (5 mM) substantially increased toxicity. Such damage was absent when catalase was present, but was still seen in the presence of superoxide dismutase. Non toxic doses of KCN (1 mM), antimycin A (1 microM), and rotenone (0.5 microM) in order to increase endogeneously produced reactive oxygen species increased toxic effects by 20-30% (p < 0.05). In our experiments we provide evidence that extracellularly produced H2O2 rather than O2-. enhances toxicity of NO. against endothelial cells. Likewise, endogeneous production of reactive oxygen species may increase toxicity of NO..
Volk
T
T
Department of Anaesthesiology and Intensive Care, University Hospital Charité, Berlin, Germany.
Ioannidis
I
I
Hensel
M
M
deGroot
H
H
Kox
W J
WJ
D000704:Analysis of Variance; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology*; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000633:toxicity; D009569:Nitric Oxide / Q000633:toxicity*; D009599:Nitroprusside / Q000633:toxicity; D010396:Penicillamine / Q000031:analogs & derivatives / Q000633:toxicity; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D012402:Rotenone / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013997:Time Factors; D014665:Vasodilator Agents / Q000633:toxicity
D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D012402:Rotenone; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D000968:Antimycin A; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D002374:Catalase; D010396:Penicillamine; D011190:Potassium Cyanide