The effect of nitric oxide release rates on the oxidation of human low density lipoprotein

1-Substituted diazen-1-ium-1,2-diolates, a class of nitric oxide (. NO) donor compounds that spontaneously release . NO at different rates, were used to investigate the effect of . NO release rate upon the oxidation of low density lipoprotein (LDL), All donor compounds conferred an inhibitory effect upon the oxidation of LDL; however, the effect exhibited a biphasic dependence upon the rate of . NO release, The . NO release rate that maximally inhibited oxidation was dependent upon the rate of oxidation, When LDL was rapidly oxidized by copper(II) sulfate, a faster release rate was more effective. In contrast, when LDL was oxidized slowly by 2,2'-azobis-2-amidinopropane hydrochloride, a slower release rate was most effective, This biphasic relationship between . NO release rate and the duration of inhibition was also demonstrated when LDL oxidation was initiated with 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium, a peroxynitrite generator, We conclude that the antioxidant ability of . NO is dependent not only upon the rate of its release from . NO donors, but also upon the rate of oxidation, This conclusion is supported by a kinetic model of LDL oxidation in the presence of . NO.