Time course of inducible nitric oxide synthase activity following endotoxin administration in dogs.
An increased production of nitric oxide (NO) via the inducible isoform of NO synthase (iNOS) has been incriminated in the pathogenesis of septic shock. Since the time course of iNOS activity is not known during endotoxic shock in dogs, we measured iNOS activity, estimated by the rate of conversion of (14)C-arginine to (14)C-citrulline in the absence of calcium, in the heart, lung, liver, kidney, and gut at 1, 2, 3, 4, and 6 h after a bolus of Escherichia coli endotoxin (2 mg/kg, iv), in the dog. This model, including generous fluid administration, is associated with typical features of human septic shock, including low systemic vascular resistance, altered myocardial function and limited oxygen extraction capability. An increase in iNOS activity was observed at 4 h in the liver (0.24 vs 0.04 mU/mg/min) and at 6 h in the heart (0.26 vs 0.09 mU/mg/min). These findings may contribute to a better delineation of the involvement of NO in endotoxic shock, and to the evaluation of the therapeutic effects of NO inhibitors.
Preiser
J C
JC
Department of Intensive Care, Erasme University Hospital, Belgium.
Zhang
H
H
Vray
B
B
Hrabak
A
A
Vincent
J L
JL
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002855:Chromatography, Thin Layer; D002956:Citrulline / Q000378:metabolism; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012772:Shock, Septic / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors
D004731:Endotoxins; D002956:Citrulline; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II