Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis.
The effects of nitric oxide (.NO) and nitrovasodilators on the oxidation of low-density lipoprotein (LDL) have been studied. S-Nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) inhibited Cu(2+)- and 2,2'-azobis-2-amidinopropane hydrochloride-dependent oxidation of LDL as monitored by oxygen consumption and the formation of thiobarbituric acid-reactive substances, conjugated dienes, and lipid hydroperoxides. In the case of SNP, inhibition of LDL oxidation occurred only when the incubation mixture was irradiated with visible light. SNAP, however, exerted a dose-dependent inhibition of Cu(2+)-catalyzed oxidation of LDL even in the dark. Addition of .NO dissolved in deoxygenated buffer also inhibited the progression of LDL oxidation. Mouse peritoneal macrophages were less able to degrade LDL that had been oxidized in the presence of SNAP. Using an .NO electrode, it was estimated that a continuous production of .NO (< or = 760 nM/min) could retard the progression of LDL oxidation. We propose that .NO can inhibit LDL oxidation by acting as a chain-breaking antioxidant that is capable of scavenging carbon-centered and peroxyl radicals. Biological implications of this novel .NO antioxidant property are discussed in relation to atherogenesis and contrasted to the prooxidant property of .NO when generated in the presence of superoxide.
Hogg
N
N
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226.
Kalyanaraman
B
B
Joseph
J
J
Struck
A
A
Parthasarathy
S
S
D000818:Animals; D003300:Copper / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008027:Light; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014665:Vasodilator Agents / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D003300:Copper; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine