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Titolo:
SELECTIVE INOS INHIBITION IS SUPERIOR TO NOREPINEPHRINE IN THE TREATMENT OF RAT ENDOTOXIC-SHOCK
Autore:
ROSSELET A; FEIHL F; MARKERT M; GNAEGI A; PERRET C; LIAUDET L;
Indirizzi:
UNIV LAUSANNE HOSP,MED CRIT CARE DIV,INST PATHOPHYSIOL,BH 05 CH-1011 LAUSANNE SWITZERLAND UNIV LAUSANNE HOSP,MED CRIT CARE DIV,INST PATHOPHYSIOL CH-1011 LAUSANNE SWITZERLAND UNIV LAUSANNE HOSP,CENT LAB CLIN CHEM CH-1011 LAUSANNE SWITZERLAND
Titolo Testata:
American journal of respiratory and critical care medicine
fascicolo: 1, volume: 157, anno: 1998,
pagine: 162 - 170
SICI:
1073-449X(1998)157:1<162:SIIIST>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; MULTIPLE ORGAN DYSFUNCTION; SEPTIC SHOCK; IMPROVES SURVIVAL; RODENT MODELS; L-ARGININE; SEPSIS; FAILURE; POTENT; OXYGEN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
A. Rosselet et al., "SELECTIVE INOS INHIBITION IS SUPERIOR TO NOREPINEPHRINE IN THE TREATMENT OF RAT ENDOTOXIC-SHOCK", American journal of respiratory and critical care medicine, 157(1), 1998, pp. 162-170

Abstract

S-methyl-isothiourea (SMT) is a potent inhibitor of NO synthase (NOS)with relative selectivity towards the inducible isoform (iNOS). We compared SMT and norepinephrine for the treatment of experimental endotoxic shock. Anaesthetized rats challenged intravenously with lipopolysaccharide (LPS), 10 mg/kg, were treated after 1 h with a 4-h infusion of norepinephrine (titrated to maintain blood pressure within baseline values), SMT at low dose (0.1 mg.kg(-1).h(-1)), or at high dose (1 mg.kg(-1).h(-1)), or an equivalent volume of saline (2 ml.kg(-1).h(-1)). In saline-treated animals, LPS increased plasma nitrate and produced hypotension, low cardiac output (CO), lactic acidosis, and signs of liver and kidney dysfunction. Norepinephrine maintained blood pressure (BP) and reduced the fall in CO, without affecting lactic acidosis, organ dysfunction, and nitrate accumulation. The latter was dose-dependently blunted by SMT. Treatment with this agent prevented hypotension, through systemic vasoconstriction with the high dose and a maintained COwith the low dose. Low, but not high, dose SMT blunted lactic acidosis. Both doses reduced the signs of renal, but not liver, dysfunction. In additional studies, we obtained evidence that, in contrast with thehigh dose, SMT at low dose did not interfere with the function of constitutive NOS. These findings suggest a potential advantage of selective iNOS inhibition over standard adrenergic support in the therapy of septic shock.

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Documento generato il 02/07/20 alle ore 22:32:12