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

• 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
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(03)02035-1

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.