title: An integrated approach to assessing nitroso-redox balance in systemic inflammation.
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. S- and 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.
authors: Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
authors: Alex
authors: A
authors: Dyson
authors: Nathan S
authors: NS
authors: Bryan
authors: Bernadette O
authors: BO
authors: Fernandez
authors: Maria-Francisca
authors: MF
authors: Garcia-Saura
authors: Fumito
authors: F
authors: Saijo
authors: Nicolas
authors: N
authors: Mongardon
authors: Juan
authors: J
authors: Rodriguez
authors: Mervyn
authors: M
authors: Singer
authors: Martin
authors: M
authors: Feelisch
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D004731:Endotoxins / Q000008:administration & dosage; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007249:Inflammation; D008297:Male; D009569:Nitric Oxide / Q000031:analogs & derivatives / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D009603:Nitroso Compounds; D009569:Nitric Oxide