L-canavanine, an inhibitor of inducible nitric oxide synthase, improves venous return in endotoxemic rats.

Détails

ID Serval
serval:BIB_603A22289309
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
L-canavanine, an inhibitor of inducible nitric oxide synthase, improves venous return in endotoxemic rats.
Périodique
Critical care medicine
Auteur⸱e⸱s
Fishman D., Liaudet L., Lazor R., Perret C.H., Feihl F.
ISSN
0090-3493
Statut éditorial
Publié
Date de publication
1997
Peer-reviewed
Oui
Volume
25
Numéro
3
Pages
469-75
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
OBJECTIVE: To investigate the hemodynamic effects of L-canavanine (an inhibitor of inducible, but not of constitutive, nitric oxide synthase) in endotoxic shock. DESIGN: Controlled, randomized, experimental study. SETTING: Animal laboratory. SUBJECTS: Wistar rats. INTERVENTIONS: Rats were anesthetized with pentobarbital, and hemodynamically monitored. One hour after an intravenous challenge with 5 mg/kg of Escherichia coli endotoxin, the rats were randomized to receive a continuous infusion of either L-canavanine (20 mg/kg/hr; n = 8) or vehicle only (isotonic saline, n = 11). In all animals, the infusion was given over 5 hrs at a rate of 2 mL/kg/hr. These experiments were repeated in additional rats challenged with isotonic saline instead of endotoxin (sham experiments). MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, heart rate, thermodilution cardiac output, central venous pressure, mean systemic filling pressure, urine output, arterial blood gases, blood lactate concentration, and hematocrit were measured. In sham experiments, hemodynamic stability was maintained throughout and L-canavanine had no detectable effect. Animals challenged with endotoxin and not treated with L-canavanine developed progressive hypotension and low cardiac output. After 6 hrs of endotoxemia, both central venous pressure and mean systemic filling pressure were significantly below their baseline values, indicating relative hypovolemia as the main determinant of reduced cardiac output. In endotoxemic animals treated with L-canavanine, hypotension was less marked, while cardiac output, central venous pressure, and mean systemic filling pressure were maintained throughout the experiment. L-canavanine had no effect on the time-course of hematocrit. L-canavanine significantly increased urine output and reduced the severity of lactic acidosis. CONCLUSIONS: Six hours after an endotoxin challenge in rats, low cardiac output develops, which appears to be primarily related to relative hypovolemia. L-canavanine, a selective inhibitor of the inducible nitric oxide synthase, increases the mean systemic filling pressure, thereby improving venous return, under these conditions.
Mots-clé
Animals, Blood Pressure, Canavanine, Cardiac Output, Disease Models, Animal, Drug Evaluation, Preclinical, Endotoxemia, Escherichia coli Infections, Male, Nitric Oxide Synthase, Random Allocation, Rats, Rats, Wistar
Pubmed
Web of science
Création de la notice
25/01/2008 9:38
Dernière modification de la notice
20/08/2019 14:17
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