Bench-to-bedside review: The role of nitric oxide in sepsis

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22 Scopus citations

Abstract

Sepsis is a state of systemic inflammation directed at microbes or their toxins in blood or tissues. Nitric oxide (NO) is one of many vasoactive molecules released from a variety of cell types during sepsis. Almost two decades ago, NO emerged as a potential therapeutic target in sepsis. NO produced by the constitutive NO synthase (NOS) isoform (endothelial NOS and neuronal NOS) in the vascular endothelium and elsewhere acts as a nonadrenergic, noncholinergic neurotransmitter, an inhibitor of platelet aggregation and a vasodilator. During sepsis, activation of inducible NOS (iNOS) in the lung epithelium and other organs occurs, leading to NO overproduction. The result of excessive circulating NO is enhanced bacterial destruction, but also profound vasodilatation, activation of inflammatory cascades and depression of cardiac function. Trials of nonselective NOS inhibitors have shown increased mean arterial pressure, but also increased pulmonary artery pressure and reduced cardiac output. Small animal studies of iNOS selective inhibition have produced dichotomous results, but larger clinical studies assessing mortality are lacking. Inhaled NO has been touted as a therapeutic option to improve systemic oxygenation in the acute lung injury of sepsis (hypoxic pulmonary vasoconstriction and pulmonary hypertension); however, studies of inhaled NO in acute respiratory distress syndrome have not shown survival efficacy. Further investigation into the role of NO in human sepsis, and the development of methods to assess NO balance in patients with sepsis is essential in this field. In this review, we outline the effects of NO in sepsis, and summarize the therapeutic outcomes of NOS inhibitors, and inhaled NO in sepsis and acute respiratory distress syndrome.

Original languageEnglish (US)
Pages (from-to)511-521
Number of pages11
JournalExpert Review of Respiratory Medicine
Volume3
Issue number5
DOIs
StatePublished - 2009

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Constitutive nitric oxide synthase
  • Endothelial nitric oxide synthase
  • Hypoxic pulmonary vasoconstriction
  • Inducible nitric oxide synthase
  • Neuronal nitric oxide synthase
  • Nitric oxide
  • Nitric oxide synthase
  • Ventilation-perfusion

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Immunology and Allergy
  • Public Health, Environmental and Occupational Health

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