Potential role of hydrogen sulfide in the pathogenesis of vascular dysfunction in septic shock

Ciro Coletta, Csaba Szabo

Research output: Contribution to journalArticle

20 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. Such dysfunction of blood vessels consists of two principal components: vascular smooth muscle (VSM) dysfunction, and endothelial dysfunction. The VSM dysfunction (progressive, therapy-resistant loss of VSM responsiveness 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 endothelium to produce nitric oxide and other 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 vascular regulatory functions of the novel gasotransmitter hydrogen sulfide (H2S), with an emphasis on its potential role in the pathogenesis of vascular dysfunction in circulatory shock. We first review the roles of endogenously produced or exogenously administered H2S on vascular function. Next, we review the results of published studies using shock models induced by bacterial lipopolysaccharide, and by cecal ligation and puncture, a polymicrobial model of sepsis showing overproduction of H2S. Finally, we summarize the potential mechanisms by which H2S may contribute to vascular dysfunction in shock and show an example of how the vascular response to H2S is altered in a rat model of endotoxemia. In addition, we outline the potential means by which modulation of H2S (pharmacological inhibition of its biosynthesis or therapeutic donation) may affect the outcome in circulatory shock.

Original languageEnglish (US)
Pages (from-to)208-221
Number of pages14
JournalCurrent Vascular Pharmacology
Volume11
Issue number2
StatePublished - 2013

Fingerprint

Hydrogen Sulfide
Septic Shock
Blood Vessels
Shock
Vascular Smooth Muscle
Gasotransmitters
Neutrophil Activation
Endotoxemia
Multiple Organ Failure
Platelet Activation
Vasoconstrictor Agents
Punctures
Endothelium
Catecholamines
Ligation
Lipopolysaccharides
Sepsis
Norepinephrine
Nitric Oxide
Perfusion

Keywords

  • Blood flow
  • cGMP
  • Circulatory shock
  • Endothelium
  • Endotoxin
  • Nitric oxide
  • Peroxynitrite
  • Sepsis
  • Smooth muscle
  • Superoxide
  • Vascular

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Potential role of hydrogen sulfide in the pathogenesis of vascular dysfunction in septic shock. / Coletta, Ciro; Szabo, Csaba.

In: Current Vascular Pharmacology, Vol. 11, No. 2, 2013, p. 208-221.

Research output: Contribution to journalArticle

@article{76418e8b40e84756b098c0f70c6563b9,
title = "Potential role of hydrogen sulfide in the pathogenesis of vascular dysfunction in septic shock",
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. Such dysfunction of blood vessels consists of two principal components: vascular smooth muscle (VSM) dysfunction, and endothelial dysfunction. The VSM dysfunction (progressive, therapy-resistant loss of VSM responsiveness 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 endothelium to produce nitric oxide and other 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 vascular regulatory functions of the novel gasotransmitter hydrogen sulfide (H2S), with an emphasis on its potential role in the pathogenesis of vascular dysfunction in circulatory shock. We first review the roles of endogenously produced or exogenously administered H2S on vascular function. Next, we review the results of published studies using shock models induced by bacterial lipopolysaccharide, and by cecal ligation and puncture, a polymicrobial model of sepsis showing overproduction of H2S. Finally, we summarize the potential mechanisms by which H2S may contribute to vascular dysfunction in shock and show an example of how the vascular response to H2S is altered in a rat model of endotoxemia. In addition, we outline the potential means by which modulation of H2S (pharmacological inhibition of its biosynthesis or therapeutic donation) may affect the outcome in circulatory shock.",
keywords = "Blood flow, cGMP, Circulatory shock, Endothelium, Endotoxin, Nitric oxide, Peroxynitrite, Sepsis, Smooth muscle, Superoxide, Vascular",
author = "Ciro Coletta and Csaba Szabo",
year = "2013",
language = "English (US)",
volume = "11",
pages = "208--221",
journal = "Current Vascular Pharmacology",
issn = "1570-1611",
publisher = "Bentham Science Publishers B.V.",
number = "2",

}

TY - JOUR

T1 - Potential role of hydrogen sulfide in the pathogenesis of vascular dysfunction in septic shock

AU - Coletta, Ciro

AU - Szabo, Csaba

PY - 2013

Y1 - 2013

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. Such dysfunction of blood vessels consists of two principal components: vascular smooth muscle (VSM) dysfunction, and endothelial dysfunction. The VSM dysfunction (progressive, therapy-resistant loss of VSM responsiveness 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 endothelium to produce nitric oxide and other 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 vascular regulatory functions of the novel gasotransmitter hydrogen sulfide (H2S), with an emphasis on its potential role in the pathogenesis of vascular dysfunction in circulatory shock. We first review the roles of endogenously produced or exogenously administered H2S on vascular function. Next, we review the results of published studies using shock models induced by bacterial lipopolysaccharide, and by cecal ligation and puncture, a polymicrobial model of sepsis showing overproduction of H2S. Finally, we summarize the potential mechanisms by which H2S may contribute to vascular dysfunction in shock and show an example of how the vascular response to H2S is altered in a rat model of endotoxemia. In addition, we outline the potential means by which modulation of H2S (pharmacological inhibition of its biosynthesis or therapeutic donation) may affect the outcome in circulatory shock.

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. Such dysfunction of blood vessels consists of two principal components: vascular smooth muscle (VSM) dysfunction, and endothelial dysfunction. The VSM dysfunction (progressive, therapy-resistant loss of VSM responsiveness 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 endothelium to produce nitric oxide and other 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 vascular regulatory functions of the novel gasotransmitter hydrogen sulfide (H2S), with an emphasis on its potential role in the pathogenesis of vascular dysfunction in circulatory shock. We first review the roles of endogenously produced or exogenously administered H2S on vascular function. Next, we review the results of published studies using shock models induced by bacterial lipopolysaccharide, and by cecal ligation and puncture, a polymicrobial model of sepsis showing overproduction of H2S. Finally, we summarize the potential mechanisms by which H2S may contribute to vascular dysfunction in shock and show an example of how the vascular response to H2S is altered in a rat model of endotoxemia. In addition, we outline the potential means by which modulation of H2S (pharmacological inhibition of its biosynthesis or therapeutic donation) may affect the outcome in circulatory shock.

KW - Blood flow

KW - cGMP

KW - Circulatory shock

KW - Endothelium

KW - Endotoxin

KW - Nitric oxide

KW - Peroxynitrite

KW - Sepsis

KW - Smooth muscle

KW - Superoxide

KW - Vascular

UR - http://www.scopus.com/inward/record.url?scp=84875327172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875327172&partnerID=8YFLogxK

M3 - Article

C2 - 23506499

AN - SCOPUS:84875327172

VL - 11

SP - 208

EP - 221

JO - Current Vascular Pharmacology

JF - Current Vascular Pharmacology

SN - 1570-1611

IS - 2

ER -