Nitric oxide--biological mediator, modulator and factor of injury: its role in the pathogenesis of atherosclerosis.

Nitric oxide (NO) is generated from L-arginine by the family of isoenzymes called NO synthases (NOS). Gene cloning has identified neuronal, endothelial and cytokine-inducible isoforms of NOS. The effects of NO depend on its microenvironment and result from interactions with oxygen, heme proteins and thiols. NO regulates vascular homeostasis by controlling vascular resistance, blood pressure, cell-cell contact and proliferation. Atherogenesis leads to decreased bioactivity of NO and this, in turn, can precipitate enhanced cell adhesion, proliferation, vasoconstriction and accelerate the generation of atherosclerotic lesions. It is possible that some of the detrimental effects of atherosclerosis on the NO pathway result from the generation of secondary oxidants such as peroxynitrite, a product of the reaction of NO with superoxide. The pharmacologic strategies including the stimulation of generation of endogenous NO, NO-replacement therapy and decreasing oxidative stress may be useful for ameliorating the clinical course of atherosclerosis.