Nitric oxide and atherosclerosis

Nitric Oxide. 2001 Apr;5(2):88-97. doi: 10.1006/niox.2001.0337.


Endothelial dysfunction has been shown in a wide range of vascular disorders including atherosclerosis and related diseases. Here, we examine and address the complex relationship among nitric oxide (NO)-mediated pathways and atherogenesis. In view of the numerous pathophysiological actions of NO, abnormalities could potentially occur at many sites: (a) impairment of membrane receptors in the arterial wall that interact with agonists or physiological stimuli capable of generating NO; (b) reduced concentrations or impaired utilization of l-arginine; (c) reduction in concentration or activity both of inducible and endothelial NO synthase; (d) impaired release of NO from the atherosclerotic damaged endothelium; (e) impaired NO diffusion from endothelium to vascular smooth muscle cells followed by decreased sensitivity to its vasodilator action; (f) local enhanced degradation of NO by increased generation of free radicals and/or oxidation-sensitive mechanisms; and (g) impaired interaction of NO with guanylate cyclase and consequent limitation of cyclic GMP production. Therefore, one target for new drugs should be the preservation or restoration of NO-mediated signaling pathways in arteries. Such novel therapeutic strategies may include administration of l-arginine/antioxidants and gene-transfer approaches.

Publication types

  • Review

MeSH terms

  • Antioxidants / therapeutic use
  • Arginine / therapeutic use
  • Arteriosclerosis / drug therapy
  • Arteriosclerosis / metabolism*
  • Arteriosclerosis / physiopathology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Humans
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / metabolism
  • Hypercholesterolemia / physiopathology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / metabolism*


  • Antioxidants
  • Nitric Oxide
  • Arginine