Acute endotoxemia inhibits microvascular nitric oxide-dependent vasodilation in humans.

Details

Serval ID
serval:BIB_05451629B8D4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Acute endotoxemia inhibits microvascular nitric oxide-dependent vasodilation in humans.
Journal
Shock
Author(s)
Engelberger R.P., Pittet Y.K., Henry H., Delodder F., Hayoz D., Chioléro R.L., Waeber B., Liaudet L., Berger M.M., Feihl F.
ISSN
1540-0514 (Electronic)
ISSN-L
1073-2322
Publication state
Published
Issued date
2011
Volume
35
Number
1
Pages
28-34
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
Nitric oxide (NO) is crucial for the microvascular homeostasis, but its role played in the microvascular alterations during sepsis remains controversial. We investigated NO-dependent vasodilation in the skin microcirculation and plasma levels of asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of the NO synthases, in a human model of sepsis. In this double-blind, randomized, crossover study, microvascular NO-dependent (local thermal hyperemia) and NO-independent vasodilation (post-occlusive reactive hyperemia) assessed by laser Doppler imaging, plasma levels of ADMA, and l-arginine were measured in seven healthy obese volunteers, immediately before and 4 h after either a i.v. bolus injection of Escherichia coli endotoxin (LPS; 2 ng/kg) or normal saline (placebo) on two different visits at least 2 weeks apart. LPS caused the expected systemic effects, including increases in heart rate (+43%, P < 0.001), cardiac output (+16%, P < 0.01), and rectal temperature (+1.4°C, P < 0.001), without change in arterial blood pressure. LPS affected neither baseline skin blood flow nor post-occlusive reactive hyperemia but decreased the NO-dependent local thermal hyperemia response, l-arginine, and, to a lesser extent, ADMA plasma levels. The changes in NO-dependent vasodilation were not correlated with the corresponding changes in the plasma levels of ADMA, l-arginine, or the l-arginine/ADMA ratio. Our results show for the first time that experimental endotoxemia in humans causes a specific decrease in endothelial NO-dependent vasodilation in the microcirculation, which cannot be explained by a change in ADMA levels. Microvascular NO deficiency might be responsible for the heterogeneity of tissue perfusion observed in sepsis and could be a therapeutic target.
Keywords
Adult, Double-Blind Method, Endothelium, Vascular/drug effects, Endothelium, Vascular/physiopathology, Endotoxemia/physiopathology, Endotoxins/toxicity, Female, Humans, Male, Microcirculation/drug effects, Microcirculation/physiology, Nitric Oxide/metabolism, Vasodilation/drug effects, Vasodilation/physiology, Young Adult
Pubmed
Web of science
Create date
09/07/2010 7:48
Last modification date
20/08/2019 12:27
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