The pivotal role of nitric oxide for vascular health

Can J Cardiol. 2004 Aug;20 Suppl B:7B-15B.


The endothelium is a single cell layer that lines all blood vessels. This tissue produces an impressive array of paracrine factors that maintain vascular homeostasis. One of these factors is the potent vasodilator endothelium-derived nitric oxide (NO). Impairment in the synthesis or bioactivity of NO, as manifested by reduced endothelium-dependent vasodilation, has been shown to be an independent risk factor for major adverse cardiovascular events. The linkage between endothelium-derived NO and cardiovascular health is likely due to the pleiotropic effects of NO on the vessel wall. NO inhibits the proliferation of vascular smooth muscle cells, the aggregation of platelets, and the adherence and infiltration of inflammatory cells. Thus, an impairment of NO bioactivity or synthesis will reduce its braking effect on processes involved in atherogenesis. New insights have been made regarding the mechanisms by which NO bioactivity becomes impaired. Cardiovascular risk factors induce vascular oxidative stress, which accelerates the degradation of NO. In addition, oxidative stress causes the accumulation of asymmetric dimethylarginine (ADMA). ADMA is an endogenous inhibitor of NO synthesis. Elevation of ADMA appears to be a common mediator by which cardiovascular risk factors impair NO synthesis. Elevation of plasma ADMA has been linked to impaired endothelium-dependent vasodilation, carotid intimal thickening and adverse cardiovascular events. A number of modern therapies directed against atherosclerosis also improve the function of the NO synthase pathway. New agents that specifically target the NO synthase pathway have been developed, and represent a new front on the war against heart disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Arteriosclerosis / physiopathology
  • Arteriosclerosis / prevention & control
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology*
  • Disease Progression
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Female
  • Homeostasis / physiology
  • Humans
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / physiology
  • Predictive Value of Tests
  • Risk Factors
  • Sensitivity and Specificity
  • Survival Analysis


  • Nitric Oxide
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase