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 Scopus citations

    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 - Mar 28 2011

    Keywords

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

    ASJC Scopus subject areas

    • Medicine(all)

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