Nitric oxide and atherosclerotic lesion progression: an overview

Abstract

There is a growing interest regarding the complex pathophysiological relationship between nitric oxide (NO) and the development of atherosclerosis. The endothelial damage induced by atherogenesis may lead to the reduction in concentration or activity both of inducible and endothelial NO synthase with subsequent impaired release of NO. Moreover, impaired NO diffusion from endothelium to vascular smooth muscle cells is followed by decreased sensitivity to its vasodilator action. Finally, an important mechanism would be a local enhanced degradation of NO by increased generation of reactive oxygen species and other free radicals with subsequent cascade of oxidation-sensitive mechanisms in the arterial wall. Therefore, one target for new drugs should be the restoration of NO-mediated signaling pathways in atherosclerotic arteries. Such novel therapeutic strategies may include administration of L-arginine, the precursor of NO, as well as antioxidants, NO donors, and tissue-specific gene-therapy approaches.