Nitric oxide and oxidative stress in vascular disease

Pflugers Arch. 2010 May;459(6):923-39. doi: 10.1007/s00424-010-0808-2. Epub 2010 Mar 21.

Abstract

Endothelium-derived nitric oxide (NO) is a paracrine factor that controls vascular tone, inhibits platelet function, prevents adhesion of leukocytes, and reduces proliferation of the intima. An enhanced inactivation and/or reduced synthesis of NO is seen in conjunction with risk factors for cardiovascular disease. This condition, referred to as endothelial dysfunction, can promote vasospasm, thrombosis, vascular inflammation, and proliferation of vascular smooth muscle cells. Vascular oxidative stress with an increased production of reactive oxygen species (ROS) contributes to mechanisms of vascular dysfunction. Oxidative stress is mainly caused by an imbalance between the activity of endogenous pro-oxidative enzymes (such as NADPH oxidase, xanthine oxidase, or the mitochondrial respiratory chain) and anti-oxidative enzymes (such as superoxide dismutase, glutathione peroxidase, heme oxygenase, thioredoxin peroxidase/peroxiredoxin, catalase, and paraoxonase) in favor of the former. Also, small molecular weight antioxidants may play a role in the defense against oxidative stress. Increased ROS concentrations reduce the amount of bioactive NO by chemical inactivation to form toxic peroxynitrite. Peroxynitrite-in turn-can "uncouple" endothelial NO synthase to become a dysfunctional superoxide-generating enzyme that contributes to vascular oxidative stress. Oxidative stress and endothelial dysfunction can promote atherogenesis. Therapeutically, drugs in clinical use such as ACE inhibitors, AT(1) receptor blockers, and statins have pleiotropic actions that can improve endothelial function. Also, dietary polyphenolic antioxidants can reduce oxidative stress, whereas clinical trials with antioxidant vitamins C and E failed to show an improved cardiovascular outcome.

Publication types

  • Review

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antioxidants / metabolism
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Aryldialkylphosphatase / metabolism
  • Biopterin / analogs & derivatives
  • Biopterin / metabolism
  • Calcium / physiology
  • Cardiovascular Diseases / etiology
  • Catalase / metabolism
  • Electron Transport / physiology
  • Glutathione Peroxidase / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Mitochondria / metabolism
  • NADPH Oxidases / metabolism
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation
  • Protein Multimerization
  • Reactive Oxygen Species / metabolism
  • Receptor, Angiotensin, Type 1
  • Renin-Angiotensin System / physiology
  • Risk Factors
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism
  • Thioredoxins / metabolism
  • Vascular Diseases / etiology
  • Vascular Diseases / physiopathology*
  • Xanthine Oxidase / metabolism

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antioxidants
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Reactive Oxygen Species
  • Receptor, Angiotensin, Type 1
  • Superoxides
  • Biopterin
  • Nitric Oxide
  • Thioredoxins
  • N,N-dimethylarginine
  • Arginine
  • Catalase
  • Glutathione Peroxidase
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Heme Oxygenase (Decyclizing)
  • Superoxide Dismutase
  • Xanthine Oxidase
  • NADPH Oxidases
  • Aryldialkylphosphatase
  • sapropterin
  • Calcium