Endothelial dysfunction in heart failure: mechanisms and therapeutic approaches

Curr Vasc Pharmacol. 2004 Apr;2(2):115-24. doi: 10.2174/1570161043476447.

Abstract

Endothelial dysfunction contributes to the development of impaired coronary and systemic perfusion as well as reduced exercise capacity in patients with congestive heart failure (CHF). Thereby endothelial dysfunction is assumed to have a fundamental impact on morbidity and potential mortality in this disease. Reduced bioavailability of nitric oxide (NO) and abundant formation of reactive oxygen species (ROS) within the vascular wall are the key determinants in endothelial dysfunction. The resulting imbalance between NO and ROS mainly results from neurohumoral activation associated with CHF. The excessive activation of the renin-angiotensin-aldosterone and endothelin systems plays a pivotal role. Treatment with ACE inhibitors, angiotensin-, aldosterone-, and endothelin-antagonists has been shown to beneficially modulate endothelial dysfunction in CHF. Furthermore, antioxidants, L-arginine, cofactors of endothelial NO-synthase, and exercise training positively modulate endothelial function. This article reviews the current knowledge of the pathophysiological events contributing to endothelial dysfunction in CHF as well as several treatment options to reverse those changes.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Arginine / metabolism
  • Biopterins / analogs & derivatives*
  • Biopterins / pharmacology
  • Disease Models, Animal
  • Endothelins / antagonists & inhibitors
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Exercise
  • Genetic Therapy
  • Heart Failure / physiopathology*
  • Heart Failure / therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type III
  • Renin-Angiotensin System / drug effects

Substances

  • Antioxidants
  • Endothelins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Biopterins
  • Nitric Oxide
  • Arginine
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • sapropterin