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Titolo:
BENEFICIAL-EFFECTS OF L-CANAVANINE, A SELECTIVE INHIBITOR OF INDUCIBLE NITRIC-OXIDE SYNTHASE, DURING RODENT ENDOTOXEMIA
Autore:
LIAUDET L; FEIHL F; ROSSELET A; MARKERT M; HURNI JM; PERRET C;
Indirizzi:
CHU VAUDOIS,INST PATHOPHYSIOL,BH 19-313 CH-1011 LAUSANNE SWITZERLAND CHU VAUDOIS,INST PATHOPHYSIOL CH-1011 LAUSANNE SWITZERLAND CHU VAUDOIS,CENT LAB CLIN CHEM CH-1011 LAUSANNE SWITZERLAND
Titolo Testata:
Clinical science
fascicolo: 5, volume: 90, anno: 1996,
pagine: 369 - 377
SICI:
0143-5221(1996)90:5<369:BOLASI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
L-ARGININE; SEPTIC SHOCK; CONTRACTION; INDUCTION; PATHWAY;
Keywords:
L-CANAVANINE; ENDOTOXIN; MOUSE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE INHIBITORS; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
L. Liaudet et al., "BENEFICIAL-EFFECTS OF L-CANAVANINE, A SELECTIVE INHIBITOR OF INDUCIBLE NITRIC-OXIDE SYNTHASE, DURING RODENT ENDOTOXEMIA", Clinical science, 90(5), 1996, pp. 369-377

Abstract

1. The cardiovascular failure in sepsis may result from increased nitric oxide biosynthesis, through the diffuse expression of an induciblenitric oxide synthase, In such conditions, nitric oxide synthase inhibitors might be of therapeutic value, but detrimental side effects have been reported with their use, possibly related to the blockade of constitutive nitric oxide synthase. Therefore, the use of selective inhibitors of inducible nitric oxide synthase might be more suitable, The aim of this study was to evaluate the effects of L-canavanine, a potentially selective inhibitor of inducible nitric oxide synthase, in an animal model of septic shock, 2. Anaesthetized rats were challenged with 10 mg/kg lipopolysaccharide intravenously, One hour later, they randomly received a 5h infusion of either L-canavanine (20 mg h(-1) kg(-1), n = 15), nitro-L-arginine methyl ester (5 mg h(-1) kg(-1), n = 13) or 0.9% NaCl (2 ml h(-1) kg(-1), n = 21), Lipopolysaccharide induced a progressive fall in blood pressure and cardiac index, accompanied by asignificant lactic acidosis and a marked rise in plasma nitrate, All these changes were significantly attenuated by L-canavanine, which also improved the tolerance of endotoxaemic animals to acute episodes of hypovolaemia. In addition, L-canavanine significantly increased survival of mice challenged with a lethal dose of lipopolysaccharide, In contrast to L-canavanine, nitro-l-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis, This agent did not improve survival of endotoxaemic mice, In additional experiments, we found that the presser effect of L-canavanine in advanced endotoxaemia (4h) was reversed by L-arginine, confirming that it was related to nitric oxide synthase inhibition, In contrast, L-canavanine did not exert any influence on blood pressure in the very early stage (first hour) of endotoxaemia or in the absence of lipopolysaccharide exposure, indicating a lack of constitutive nitric oxide synthase inhibition by this agent, 3. In conclusion, L-canavanine produced beneficial haemodynamic and metabolic effects and improved survival in rodent endotoxic shock, The actions of L-canavanine were associated with a selective inhibition of inducible nitric oxide synthase and were in marked contrast to the deleterious consequences of nitro-L-arginine methyl ester, a non-selective nitric oxidesynthase inhibitor, in similar conditions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 06:58:28