ENDOTHELIAL DAMAGE-INDUCED BY NITRIC-OXIDE - SYNERGISM WITH REACTIVE OXYGEN SPECIES

Interactions of reactive oxygen and nitrogen species to mediate endoth elial cell damage were studied in vitro. S-Nitroso-N-acetyl-DL-penicil lamine (SNAP), 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) and so diumnitroprusside (SNP) were used as NO .-donating agents, The toxicit y of SIN-1 (5 mM), which produces both O-2(-). and NO, was reduced whe n catalase was added to remove H2O2 whereas superoxide dismutase had a marginal protective influence, Low doses of H2O2 producing enzymes ad ded to low doses of SNAP (1 mM) or SNP (5 mM) substantially increased toxicity, Such damage was absent when catalase was present, but was st ill seen in the presence of superoxide dismutase, Non toxic doses of K CN (1 mM), antimycin A (1 mu M), and rotenone (0.5 mu M) in order to i ncrease 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 O-2(-). enhances toxic ity of NO . against endothelial cells, Likewise, endogeneous productio n of reactive oxygen species may increase toxicity of NO .. (C) 1995 A cademic Press, Inc.