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 language | English (US) |
|---|---|
| Pages (from-to) | 1-16 |
| Number of pages | 16 |
| Journal | Journal of Medical Sciences |
| Volume | 31 |
| Issue number | 1 |
| State | Published - 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Role of nitric oxide in the development of vascular contractile dysfunction in circulatory shock
AU - Szabo, Csaba
AU - Wu, Chin Chen
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - cGMP
KW - Circulatory shock
KW - Nitric oxide
KW - Sepsis
KW - Superoxide
UR - http://www.scopus.com/inward/record.url?scp=79952936147&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952936147&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:79952936147
VL - 31
SP - 1
EP - 16
JO - Journal of Medical Sciences (Taiwan)
JF - Journal of Medical Sciences (Taiwan)
SN - 1011-4564
IS - 1
ER -