L-canavanine improves organ function and tissue adenosine triphosphate levels in rodent endotoxemia

Details

Serval ID
serval:BIB_9804D8140ABB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
L-canavanine improves organ function and tissue adenosine triphosphate levels in rodent endotoxemia
Journal
American Journal of Respiratory and Critical Care Medicine
Author(s)
Liaudet  L., Fishman  D., Markert  M., Perret  C., Feihl  F.
ISSN
1073-449X (Print)
Publication state
Published
Issued date
05/1997
Volume
155
Number
5
Pages
1643-8
Notes
Journal Article --- Old month value: May
Abstract
Overproduction of NO by an inducible NO synthase (iNOS) plays a major role in the pathophysiology of septic shock, and selective inhibition of iNOS in this setting could be of great therapeutic value. In the present study, we evaluated the effects of L-canavanine, a selective iNOS inhibitor, in an animal model of septic shock, with a particular focus on tissue oxidative metabolism and organ functions. Anesthetized rats challenged intravenously with lipopolysacharide (LPS) were treated after 1 h by a continuous infusion of either L-canavanine (20 mg/kg/h; n = 11) or an equivalent volume of saline (2 ml/kg/h; n = 17) given for 4 h. A third group (sham rats; n = 9) did not receive LPS and was treated with a continuous infusion of saline (2 ml/kg/h). At the end of experiments, biopsies were taken from the liver, the kidney, and the small intestine for the measurement of tissue ATP. LPS induced a progressive fall in blood pressure, accompanied by biologic signs of liver and kidney failure, concomitant with a marked decrease in tissue ATP stores. L-canavanine largely prevented hypotension and significantly increased tissue ATP while reducing the signs of organ dysfunction. These effects were associated with a significant improvement in survival during the 5 h of study. We conclude that L-canavanine not only reduces hypotension in endotoxin shock but also largely prevents the detrimental consequences of LPS on tissue oxidative metabolism and major organ functions, allowing a decrease in endotoxin lethality.
Keywords
Adenosine Triphosphate/*metabolism Animals Blood Pressure/drug effects Canavanine/*pharmacology Endotoxemia/*metabolism Escherichia coli Intestine, Small/metabolism Kidney/metabolism Lipopolysaccharides Liver/metabolism Male Nitric Oxide/metabolism Nitric Oxide Synthase/*antagonists & inhibitors Rats Rats, Wistar Shock, Septic/*metabolism/physiopathology
Pubmed
Web of science
Create date
25/01/2008 9:38
Last modification date
20/08/2019 14:59
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