Reactivity of peroxynitrite and nitric oxide with LDL

Low density lipoprotein (LDL) oxidation by peroxynitrite is a complex process, finely modulated by control of peroxynitrite formation, LDL availability and free-radical scavenging by nitric oxide ((NO)-N-center dot), ascorbate and alpha-tocopherol (alpha-TOH). In the presence of CO2, lipid targets are spared at the expense of surface constituents. Since surface damage may lead to oxidation-induced LDL aggregation and particle recognition by scavenger receptors, CO2 cannot be considered an inhibitor of peroxynitrite-dependent LDL modi. cations. Chromanols, urate and ascorbate cannot scavenge peroxynitrite in the vasculature, although intermediates of urate oxidation and high ascorbate concentrations may do so in vitro. Most if not all of the protection against peroxynitrite-induced LDL oxidation afforded by urate, ascorbate, chromanols and also (NO)-N-center dot should be considered to depend on their free radical scavenging abilities, including inactivation of lipid peroxyl radicals ( LOO), (NO2)-N-center dot, and CO3 center dot-; as well as their capacity to reduce high oxidation states of metal centers. Peroxynitrite direct interception by reduced manganese (II) porphyrins is possibly the most powerful although unspecific strategy to inhibit peroxynitrite reactions. In light of the recent demonstration of nitrated bioactive lipids in vivo, renewed interest in the mechanisms of peroxynitrite- and nitric oxide-mediated lipid nitration and nitrosation is guaranteed.