Inhaled NO reduces leukocyte-endothelial cell interactions and myocardial dysfunction in endotoxemic rats

Nevière, Rémi; Guery, Benoît; Mordon, Serge; Zerimech, Farid; Charre, S; Wattel, F; Chopin, C.

doi:10.1152/ajpheart.2000.278.6.h1783

Cited by 24 publications

(17 citation statements)

References 42 publications

(53 reference statements)

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“…Previous work to define the role of NO under these circumstances has produced variable results, which is particularly true for the lung. NO-related mechanisms that may protect against inflammatory injury in this organ include vasodilation (26 -28) and suppression of leukocyte adhesion to the pulmonary endothelium as well as leukocyte activation (29). In lung ischemiareperfusion models, inhalation of NO was shown to suppress the vasoconstrictor response and pulmonary edema formation, as well as ventilation-perfusion mismatch and shunt flow (30 -34).…”

Section: Discussionmentioning

confidence: 99%

Apical, But Not Basolateral, Endotoxin Preincubation Protects Alveolar Epithelial Cells Against Hydrogen Peroxide-Induced Loss of Barrier Function: The Role of Nitric Oxide Synthesis

Rose

Guthmann

Tenenbaum

et al. 2002

The Journal of Immunology

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The influence of LPS preincubation on hydrogen peroxide (H2O2)-induced loss of epithelial barrier function was investigated in rat alveolar epithelial type II cells (ATII). Both apical and basolateral H2O2 administration caused a manyfold increase in transepithelial [3H]mannitol passage. Apical but not basolateral preincubation of ATII with LPS did not influence control barrier properties but fully abrogated the H2O2-induced leakage response. The effect of apical LPS was CD14 dependent and was accompanied by a strong up-regulation of NO synthase II mRNA and protein and NO release. Inhibition of NO by NG-monomethyl-l-arginine suppressed the LPS effect, whereas it was reproduced by exogenous application of gaseous NO or NO donor agents. Manipulation of the glutathione homeostasis (buthionine-(S,R)-sulfoximine) and the cGMP pathway (1H-(1,2,4)oxadiazolo[4,3-α]quinoxaline-1-one; zaprinast) did not interfere with the protective effect of LPS. Superoxide (O⨪2) generation by ATII cells was reduced by exogenous NO and LPS preincubation. O⨪2 scavenging with exogenous superoxide dismutase, the intracellular superoxide dismutase analog Mn(III)tetrakis(4-benzoic acid) porphyrin, and the superoxide scavenger nitroblue tetrazolium and, in particular, hydroxyl radical scavenging with hydroxyl radical scavenger 1,3-dimethyl-thiourea inhibited the H2O2-induced epithelial leakage response. In conclusion, apical but not basolateral LPS preincubation of ATII cells provides strong protection against H2O2-induced transepithelial leakage, attributable to an up-regulation of epithelial NO synthesis. It is suggested that the LPS-induced NO formation is effective via interaction with reactive oxygen species, including superoxide and hydroxyl radicals. The polarized epithelial response to LPS may be part of the lung innate immune system, activated by inhaled endotoxin or under conditions of pneumonia.

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Section: Discussionmentioning

confidence: 99%

Apical, But Not Basolateral, Endotoxin Preincubation Protects Alveolar Epithelial Cells Against Hydrogen Peroxide-Induced Loss of Barrier Function: The Role of Nitric Oxide Synthesis

Rose

Guthmann

Tenenbaum

et al. 2002

The Journal of Immunology

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“…Under basal conditions, ⅐ NO plays a central role in maintaining vascular homeostasis (56)(57)(58)(59). Thus, stimulation of ⅐ NO consumption by monocytes will contribute to proatherogenic conditions by increasing leukocyte adhesion and margination.…”

Section: Discussionmentioning

confidence: 99%

Catalytic consumption of nitric oxide by 12/15- lipoxygenase: Inhibition of monocyte soluble guanylate cyclase activation

Coffey

Natarajan

Chumley

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…94 After cecal ligation and double puncture, myocardial intercellular adhesion molecule-1 expression increases in rats. 95 Vascular cell adhesion molecule-1 blockade with antibodies has been shown to prevent myocardial dysfunction and decrease myocardial neutrophil accumulation, 94,96 whereas both knockout and antibody blockade of intercellular adhesion molecule-1 ameliorate myocardial dysfunction in endotoxemia without affecting neutrophil accumulation. 94 In addition, neutrophil depletion does not protect against septic cardiomyopathy, which suggests that the cardiotoxic potential of neutrophils infiltrating the myocardium is of lesser importance in this context.…”

Section: Adhesion Moleculesmentioning

confidence: 99%

Sepsis and the Heart

2007

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Abstract-Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur. A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others. Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. Morbidity and mortality are high, resulting in sepsis and septic shock being the 10th most common cause of death in the United States. 5 The incidence of sepsis and sepsis-related deaths appears to be increasing by 1.5% per year. 6 In a recent study, 6 the total national hospital cost invoked by severe sepsis in the United States was estimated at approximately $16.7 billion on the basis of an estimated severe sepsis rate of 751 000 cases per year with 215 000 associated deaths annually. A recent study from Britain documented a 46% in-hospital mortality rate for patients presenting with severe sepsis on admission to the intensive care unit. 7 As an important organ system frequently affected by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. In 1951, Waisbren was the first to describe cardiovascular dysfunction due to sepsis. 8 He recognized a hyperdynamic state with full bounding pulses, flushing, fever, oliguria, and hypotension. In addition, he described a second, smaller patient group who presented clammy, pale, and hypotensive with low volume pulses and who appeared more severely ill. With hindsight, the latter group might well have been volume underresuscitated...

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Inhaled NO reduces leukocyte-endothelial cell interactions and myocardial dysfunction in endotoxemic rats

Cited by 24 publications

References 42 publications

Apical, But Not Basolateral, Endotoxin Preincubation Protects Alveolar Epithelial Cells Against Hydrogen Peroxide-Induced Loss of Barrier Function: The Role of Nitric Oxide Synthesis

Apical, But Not Basolateral, Endotoxin Preincubation Protects Alveolar Epithelial Cells Against Hydrogen Peroxide-Induced Loss of Barrier Function: The Role of Nitric Oxide Synthesis

Catalytic consumption of nitric oxide by 12/15- lipoxygenase: Inhibition of monocyte soluble guanylate cyclase activation

Sepsis and the Heart

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