Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock.
J Infect Dis
; 177(1): 127-32, 1998 Jan.
Article
em En
| MEDLINE
| ID: mdl-9419179
ABSTRACT
The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-gamma-L-arginine methyl ester (L-NAME, nonselective NOS inhibitor, 10-60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50-300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this setting.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Canavanina
/
Óxido Nítrico Sintase
/
NG-Nitroarginina Metil Éster
/
Inibidores Enzimáticos
Limite:
Animals
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
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