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 isoenz ymes 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 oxyge n, heme proteins and thiols. NO regulates vascular homeostasis by cont rolling vascular resistance, blood pressure, cell-cell contact and pro liferation. Atherogenesis leads to decreased bioactivity of NO and thi s, in turn, can precipitate enhanced cell adhesion, proliferation, vas oconstriction and accelerate the generation of atherosclerotic lesions . It is possible that some of the detrimental effects of atheroscleros is 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 str ess may be useful for ameliorating the clinical course of atherosclero sis.