Comparative effects of dexamethasone and l-canavanine in experimental septic shock

Glucocorticoids can reverse hemodynamic disturbances and dependence on catecholamines in septic shock. The relevant beneficial mechanisms of steroids in septic shock are unknown, although inducible nitric oxide synthase could account for them. The aim of this study was to compare the effects of dexa...

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Bibliographic Details
Published in:European journal of pharmacology 2003-08, Vol.475 (1), p.61-67
Main Authors: Mansart, Arnaud, Bollaert, Pierre-Edouard, Levy, Bruno, Nicolas, Marie-Bénédicte, Mallié, Jean-Pierre
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Pressure - drug effects
Blood Pressure - physiology
Canavanine - pharmacology
Canavanine - therapeutic use
Cardiovascular system
Dexamethasone - pharmacology
Dexamethasone - therapeutic use
Heart Rate - drug effects
Heart Rate - physiology
Hemodynamic
Male
Medical sciences
Miscellaneous
Nitric oxide (NO)
Pharmacology. Drug treatments
Rats
Rats, Wistar
Regional Blood Flow - drug effects
Regional Blood Flow - physiology
Sepsis
Shock, Septic - drug therapy
Shock, Septic - physiopathology
Steroid
Survival Rate
Vasopressor
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Summary:Glucocorticoids can reverse hemodynamic disturbances and dependence on catecholamines in septic shock. The relevant beneficial mechanisms of steroids in septic shock are unknown, although inducible nitric oxide synthase could account for them. The aim of this study was to compare the effects of dexamethasone, a glucocorticoid and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in a rodent model of sepsis. Mean arterial pressure was restored by dexamethasone and l-canavanine administration at 24 h, no longer at 30 h. Dexamethasone but not l-canavanine improved aortic blood flow at 24 and 30 h. Although both dexamethasone and l-canavanine administration significantly reduced nitrite/nitrate production, and improved survival, steroids did better for survival. In conclusion, dexamethasone and l-canavanine displayed similar vasopressor effects. In addition, steroids improved blood flow suggesting that steroid-induced hemodynamic improvement in sepsis is not solely due to inhibition of inducible nitric oxide synthase.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(03)02035-1