The nitric oxide congener nitrite inhibits myeloperoxidase/H2O2/Cl--mediated modification of low density lipoprotein

Nitric oxide, a pivotal molecule in vascular homeostasis, is converted unde r aerobic conditions to nitrite. Recent studies have shown that myeloperoxi dase (MPO), an abundant heme protein released by activated leuko- cytes, ca n oxidize nitrite (NO,) to a radical species, most likely nitrogen dioxide. Furthermore, hypochlorous acid (HOCl), the major strong oxidant generated by MPO in the presence of physiological concentrations of chloride ions, ca n also react with nitrite, forming the reactive intermediate nitryl chlorid e. Since MPO and MPO derived HOCl, as well as reactive nitrogen species, ha ve been implicated in the pathogenesis of atherosclerosis through oxidative modification of low density lipoprotein (LDL), we investigated the effects of physio logical concentrations of nitrite (12.5-200 muM) on MPO-mediated modification of LDL in the absence and presence of physiological chloride concentrations. Interestingly, nitrite concentrations as low as 12.5 and 25 muM significantly decreased MPO/H2O2/Cl--induced modification of apoB lysi ne residues, formation of N-chloramines, and increases in the relative elec trophoretic mobility of LDL. In contrast, none of these markers of LDL athe rogenic modification were affected by the MPO/ H2O2/NO2- system. Furthermor e, experiments using ascorbate (12.5-200 ECM) and the tyrosine analogue 4-h ydroxyphenylacetic acid (12.5-200 muM), which are both substrates of MPO, i ndicated that nitrite inhibits MPO-mediated LDL modifications by trapping t he enzyme in its inactive compound II form. These data offer a novel mechan ism for a potential antiatherogenic effect of the nitric oxide congener nit rite.