title: Nitric oxide-derived nitrate anion contributes to endotoxic shock and multiple organ injury/dysfunction.
abstract: OBJECTIVE
  Because nitrate represents the major end-product of nitric oxide in vivo and can affect enzyme activity, cell electrophysiological functions, and cell membrane integrity, we hypothesized that overaccumulated nitric oxide-derived nitrate anion in tissues or organs in vivo may contribute to endotoxic shock and multiple organ injury/dysfunction during endotoxemia.
  
  
  METHODS
  Prospective, experimental animal study.
  
  
  METHODS
  Laboratory at a university hospital.
  
  
  METHODS
  Sprague-Dawley rats.
  
  
  METHODS
  Rats were injected intraperitoneally with 5, 10, or 20 mg/kg lipopolysaccharide or saline and were studied in groups at 0, 6, 12, and 24 hrs.
  
  
  RESULTS
  Significant differences were seen between nitrate concentrations in the heart, lung, kidney, liver, brain, aorta, diaphragm, spleen, thymus, testis or ovary, hind limb muscle, intestine, adipose tissue, bone, bladder, urine and plasma, which imply a nitrate gradient between intracellular and extracellular compartments. Lipopolysaccharide significantly increased nitrate concentration at 12 hrs in most tissues and organs, except in the brain, adipose tissue, and muscle. It increased more in plasma than in tissues. The lipopolysaccharide dose-dependent nitrate concentration was observed only in the aorta and lungs. The nitrate concentration change was paralleled by the systemic inflammatory response syndrome, as indicated by alterations of myeloperoxidase activity and by impaired histologic and cellular membrane integrity in tissues and organs. Mean arterial pressure was negatively correlated with nitrate concentration modifications in the aorta during 24 hrs of endotoxemia.
  
  
  CONCLUSIONS
  These results collectively indicate that overaccumulated nitric oxide-derived nitrate anion in tissues or organs in vivo contributes to endotoxic shock and multiple organ injury/dysfunction during endotoxemia.
authors: Laboratory of Anesthesia, Centre hospitalier de l'Université de Montréal-Hôpital Notre-Dame and Université de Montréal, Québec, Canada. fan.yang@umontreal.ca
authors: Fan
authors: F
authors: Yang
authors: Alain Steve
authors: AS
authors: Comtois
authors: Liwei
authors: L
authors: Fang
authors: Neil Godfried
authors: NG
authors: Hartman
authors: Gilbert
authors: G
authors: Blaise
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002463:Cell Membrane Permeability; D019446:Endotoxemia / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics; D008070:Lipopolysaccharides; D009102:Multiple Organ Failure / Q000473:pathology / Q000503:physiopathology*; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009569:Nitric Oxide; D009195:Peroxidase