Dyson, Alex, Bryan, Nathan S., Fernandez, Bernadette O., Garcia-Saura, Maria Francisca, Saijo, Fumito, Mongardon, Nicolas, Rodriguez, Juan, Singer, Mervyn and Feelisch, Martin. (2011) An integrated approach to assessing nitroso-redox balance in systemic inflammation. Free Radical Biology and Medicine, Vol.51 (No.6). pp. 1137-1145. ISSN 0891-5849

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Abstract

Most studies examining the metabolic fate of NO during systemic inflammation have focused on measuring the quantitatively predominating, stable anions nitrite and nitrate within the circulation. However, these are not necessarily the NO-related products that govern NO metabolism and signaling in tissues. We assessed all major NO derivatives temporally in blood and vital organs during inflammation and explored their relationship to insult severity and redox status. Male rats receiving intraperitoneal endotoxin or vehicle were sacrificed for organ and blood sampling between 0 and 24 h. Endotoxin induced transient and organ-specific changes in a variety of NO metabolites. Nitrite and nitrate increased, peaking at 8 and 12 h, respectively. Sand N-nitrosation and heme-nitrosylation products also peaked at 8 h; these posttranslational protein modifications were associated with decreased myocardial function (echocardiography). Evidence of oxidative stress and systemic inflammation was also obtained. The rise in most NO derivatives was proportional to insult severity. All metabolite levels normalized within 24 h, despite evidence of persisting myocardial dysfunction and clinical unwellness. Our findings point to a complex interplay between NO production, antioxidant defense, and redox status. Although the precise (patho)physiologic roles of specific NO derivatives and their diagnostic/prognostic utility await further investigation, nitroso species in erythrocytes are the most sensitive markers of NO in systemic inflammation, detectable before clinical symptoms manifest.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Nitrosation, Endotoxins, Septicemia, Nitric oxide, Free radicals (Chemistry), Nitrogen compounds
Journal or Publication Title:	Free Radical Biology and Medicine
Publisher:	Elsevier Science Inc.
ISSN:	0891-5849
Official Date:	15 September 2011
Dates:	Date Event 15 September 2011 Published
Volume:	Vol.51
Number:	No.6
Page Range:	pp. 1137-1145
Identification Number:	10.1016/j.freeradbiomed.2011.06.012
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	National Institutes of Health (U.S.) (NIH), Ruth L. Kirschstein Cardiovascular Training Grant , Medical Research Council (Great Britain) (MRC), National Institute for Health Research (Great Britain) (NIHR)
Grant number:	HL 69029 (NIH)
URI:	http://wrap.warwick.ac.uk/id/eprint/38360

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