Nitric oxide and its role in lipid peroxidation

Nitric oxide (NO) is a free radical with an unpaired electron in the highest orbital. This is why it behaves as a potential antioxidant agent by virtue of its ability to reduce other molecules. In vitro experiments support this concept inasmuch as NO is able to inhibit lipid peroxidation. However, NO is rapidly inactivated by the superoxide anion (O(*2) to form peroxynitrite (ONOO-), which is a potent oxidant. Therefore, in the presence of O(*2), NO behaves as a potent pro-oxidant. This is the mechanism that accounts for the low density lipoprotein (LDL) oxidation that occurs when NO and O(*2) are simultaneously present in the medium. As NO and O(*2) are simultaneously released by cells such as endothelial cells, the balance between these two radicals is crucial in understanding the net effect of NO on lipid peroxidation. Thus an excess of NO will favour lipid peroxidation inhibition, while an excess of O(*2) or equimolar concentration of NO and O(*2) will induce lipid peroxidation. Modulation of this balance may have important clinical implications, particularly in the atherosclerotic process in which oxidant stress seems to play a pivotal role in the onset and progression of vascular lesions.