Role of nitric oxide in the development of vascular contractile dysfunction in circulatory shock

Csaba Szabo, Chin Chen Wu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Various forms of circulatory shock (including septic shock) lead to an impairment of vascular function, which importantly contributes to the development of multiple organ failure and mortality. The dysfunction of the blood vessels in shock consists of two principal components: vascular smooth muscle dysfunction, and endothelial dysfunction. The vascular smooth muscle dysfunction (a progressive, therapy-resistant loss of responsiveness of the vascular smooth muscle to vasoconstrictor catecholamines, such as noradrenaline) leads to a progressive deterioration of blood pressure in patients with circulatory shock. The endothelial dysfunction (loss of the ability of the vascular endothelium to produce nitric oxide and other local endothelium-derived factors) contributes to the impairment of microvascular blood flow, to the enhanced adhesion and activation of neutrophils and platelets, to coagulation problems, and perfusion/metabolism mismatch in the affected organs. Here we overview the role of nitric oxide (NO) in the pathogenesis of vascular contractile dysfunction in circulatory shock. We describe the results of published studies involving shock models induced by bacterial lipopolysac-charide (LPS), and by cecal ligation and puncture (CLP), a polymicrobial model of sepsis. Among the many contributing factors, we focus on the role of cyclic GMP (cGMP) dependent pathways as well as a number of cGMP independent pathways. We will also outline the role of oxidative/nitrosative stress, peroxynitrite and poly(ADP-ribose) polymerase (PARP) and vascular potassium channels in the sepsis-associated alterations in vascular smooth muscle contractility.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalJournal of Medical Sciences
Volume31
Issue number1
StatePublished - 2011

Fingerprint

Blood Vessels
Shock
Nitric Oxide
Vascular Smooth Muscle
Cyclic GMP
Sepsis
Neutrophil Activation
Peroxynitrous Acid
Multiple Organ Failure
Poly(ADP-ribose) Polymerases
Potassium Channels
Platelet Activation
Vascular Endothelium
Vasoconstrictor Agents
Septic Shock
Punctures
Endothelium
Catecholamines
Ligation
Norepinephrine

Keywords

  • cGMP
  • Circulatory shock
  • Nitric oxide
  • Sepsis
  • Superoxide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Role of nitric oxide in the development of vascular contractile dysfunction in circulatory shock. / Szabo, Csaba; Wu, Chin Chen.

In: Journal of Medical Sciences, Vol. 31, No. 1, 2011, p. 1-16.

Research output: Contribution to journalArticle

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