Pathophysiological roles of peroxynitrite in circulatory shock

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide, which reacts with proteins, lipids, and DNA, and promotes cytotoxic and proinflammatory responses. Here, we overview the role of peroxynitrite in various forms of circulatory shock. Immunohistochemical and biochemical evidences demonstrate the production of peroxynitrite in various experimental models of endotoxic and hemorrhagic shock both in rodents and in large animals. In addition, biological markers of peroxynitrite have been identified in human tissues after circulatory shock. Peroxynitrite can initiate toxic oxidative reactions in vitro and in vivo. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na/K ATPase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of peroxynitrite. In addition, peroxynitrite is a potent trigger of DNA strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) polymerase, which promotes cellular energetic collapse and cellular necrosis. Additional actions of peroxynitrite that contribute to the pathogenesis of shock include inactivation of catecholamines and catecholamine receptors (leading to vascular failure) and endothelial and epithelial injury (leading to endothelial and epithelial hyperpermeability and barrier dysfunction), as well as myocyte injury (contributing to loss of cardiac contractile function). Neutralization of peroxynitrite with potent peroxynitrite decomposition catalysts provides cytoprotective and beneficial effects in rodent and large-animal models of circulatory shock.

Original languageEnglish (US)
Pages (from-to)4-14
Number of pages11
JournalShock
Volume34
Issue numberSUPPL. 1
DOIs
StatePublished - Sep 2010

Fingerprint

Peroxynitrous Acid
Shock
Rodentia
Catecholamine Receptors
Glyceraldehyde-3-Phosphate Dehydrogenases
Enzyme Activation
Poly(ADP-ribose) Polymerases
Hemorrhagic Shock
Sodium Channels
Poisons
DNA
Wounds and Injuries
Septic Shock
Electron Transport
Ion Channels
Oxidants
Superoxides
Muscle Cells
Lipid Peroxidation
Catecholamines

Keywords

  • contraction
  • endotoxin
  • inflammation
  • Nitric oxide
  • poly(ADP-ribose) polymerase
  • superoxide
  • vascular dysfunction

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Pathophysiological roles of peroxynitrite in circulatory shock. / Szabo, Csaba; Modis, Katalin.

In: Shock, Vol. 34, No. SUPPL. 1, 09.2010, p. 4-14.

Research output: Contribution to journalArticle

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