The influence of organic peroxides on platelet aggregation and sensitivityto nitric oxide

The effects of oxidative stress, induced by water-soluble and lipid peroxid es, on platelet reactivity and platelet sensitivity to nitric oxide mere in vestigated. Hydrogen peroxide and cumene hydroperoxide potentiated thrombin -induced platelet aggregation. In contrast, 15(S)-hydroperoxyeicosatetraeno ic acid had no such effect, while 12(S)-hydroperoxyeicosatetraenoic acid in hibited platelet reactivity, All of the peroxides tested mere found to decr ease platelet sensitivity to nitric oxide, although the mechanisms by which the various peroxides altered platelet sensitivity to nitric oxide were di fferent. The water-soluble peroxides opposed the actions of nitric oxide wi thout affecting cyclic GMP levels, while 15(S)-hydroperoxyeicosatetraenoic acid caused a significant reduction in the concentration of cyclic GMP form ed in response to NO, The data from this study demonstrate that water-solub le and lipid peroxides both affect platelet reactivity and regulation, but by different mechanisms. Thus, caution should be exercised when selecting p eroxides to be used as models of oxidative stress.