INHIBITION OF MACROPHAGE-DEPENDENT LOW-DENSITY-LIPOPROTEIN OXIDATION BY NITRIC-OXIDE DONORS

We have previously shown that nitric oxide donors inhibit the oxidatio n of low density lipoprotein (LDL) initiated by copper ions or by azo- bis-amidinopropane (Hogg et al., 1993. FEES Lett, 334: 170-174). In th is study, the nitric oxide donors S-nitroso-N-acetylpenicillamine (SNA P), spermine NONOate, and sodium nitroprusside were tested for their a bility to inhibit macrophage-dependent oxidation of LDL. SNAP and sper mine NONOate inhibited macrophage-dependent oxidation of LDL in a time - and concentration-dependent manner. We propose that nitric oxide is acting as a chain-breaking antioxidant that can inhibit the progressio n of lipid peroxidation in cell dependent-oxidation of LDL. By this me chanism nitric oxide could be an endogenous defense against atherogene sis. In contrast, sodium nitroprusside enhanced cell-mediated oxidatio n of LDL by a mechanism dependent on superoxide production and transit ion metal ions. Sodium nitroprusside also enhanced LDL oxidation by ce ll culture medium alone by a similar mechanism. The use of sodium nitr oprusside as a nitric oxide donor in cellular systems appears to be co mplicated by the release of iron leading to an enhanced oxidative stre ss. Thus the effects of sodium nitroprusside in such systems may be un related to nitric oxide release.