NITRIC-OXIDE ATTENUATES HYDROGEN PEROXIDE-MEDIATED INJURY TO PORCINE PULMONARY-ARTERY ENDOTHELIAL-CELLS

To examine the role of nitric oxide (. NO) in vascular endothelial cel l injury, cultured porcine pulmonary artery endothelial cells (PAEC) w ere treated with H2O2 (100-500 mu M) for 30 min in the presence or abs ence of the . NO donors (+/-)S-nitrosa-N-acetylpenicillamine (SNAP) or diethylamine nitric oxide (DEANO). H2O2 caused dose-dependent PAEC cy totoxicity detected 2 h after H2O2 treatment as the release of lactate dehydrogenase. SNAP(100 mu M) and DEANO (100 mu M) attenuated H2O2-in duced cytotoxicity if present during H2O2 treatment. In contrast, rest ricting 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 N-G-nitro-L-arginine methyl ester (1 mM) s ensitized PAEC to H2O2-induced injury. SNAP also attenuated H2O2- indu ced PAEC lipid peroxidation even if restricted to periods before or af ter 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.