Effect of nitric oxide donors and nitric oxide synthase inhibitors in neonatal rat endotoxic shock.
Biochem Pharmacol
; 58(4): 687-91, 1999 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-10413307
ABSTRACT
Previous studies have shown an increased mortality in response to endotoxin in 24-hr-old neonatal rats compared with older neonates and adults. This increased susceptibility may be related to increased nitric oxide (NO) and thromboxane (TxB2) production. Twenty-four-hour-old neonatal rat pups were given either N(G)-nitro-L-arginine methyl ester (L-NAME; a nonspecific NO synthase inhibitor), S-methylthioisourea (SMT; a specific NO synthase inhibitor), or molsidomine (a NO donor) subcutaneously prior to or after an LD50 of intracardiac endotoxin. Mortality was followed for 72 hr. There was no statistically significant difference in mortality between control animals and those pretreated with L-NAME, SMT, or molsidomine. A trend toward increased mortality with nonspecific NO synthase inhibition and decreased mortality with the NO donor was noted. Splenic cells were obtained for in vitro cytokine stimulation studies. In vitro adherent splenic cell stimulation studies confirmed an increase in NO production with NO donor pretreatment and decreased production of NO with NO synthase inhibition pretreatment. There was no difference in TxB2 production with either the NO synthase inhibitor or the NO donor. In conclusion, at the several doses employed, neither nonselective or selective NO synthase inhibitors nor NO donors prevented endotoxin-induced mortality in rat neonatal shock. Although these findings do not preclude possible involvement of NO in neonatal pathophysiology, increased NO production thus does not appear to be the primary determinant of the increased susceptibility of the neonatal rat to endotoxic shock.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Óxido Nítrico Sintase
/
Doadores de Óxido Nítrico
/
Inibidores Enzimáticos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1999
Tipo de documento:
Article