Nitric oxide-derived nitrate anion contributes to endotoxic shock and multiple organ injury/dysfunction.
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.
Yang
Fan
F
Laboratory of Anesthesia, Centre hospitalier de l'Université de Montréal-Hôpital Notre-Dame and Université de Montréal, Québec, Canada. fan.yang@umontreal.ca
Comtois
Alain Steve
AS
Fang
Liwei
L
Hartman
Neil Godfried
NG
Blaise
Gilbert
G
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
D008070:Lipopolysaccharides; D009566:Nitrates; D009569:Nitric Oxide; D009195:Peroxidase