Expression of inducible nitric oxide synthase in mice: pharmacological evaluation of adenosine receptor agonists

European Journal of Pharmacology
S MoochhalaH E Khoo

Abstract

Inhibition of inducible nitric oxide (NO) synthase during endotoxaemia may be of therapeutic value. We have previously shown that pretreatment of mice with adenosine receptor agonists 1 h before lipopolysaccharide administration results in a dose-dependent reduction of plasma nitrite and nitrate (NOx-) levels. This report examines the effects of adenosine receptor agonists, 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA), R-phenylisopropyl-adenosine (R-PIA) and 5'-(N-cyclopropyl)carboxamidoadenosine (CPCA), on the level of inducible NO synthase expression in a model of liver inflammation induced by lipopolysaccharide. Following lipopolysaccharide administration (10 mg/kg, i.p.), liver mRNA expression peaked at 3 h and declined to 35% of maximal level after 24 h. Pretreatment with adenosine receptor agonists (0.001 mg/kg to 5 mg/kg, i.p.) depressed inducible NO synthase mRNA expression significantly. Down-regulation of inducible NO synthase mRNA expression corresponded with changes in plasma NOx- level as well as activity of NO synthase in the liver. Administration of R-PIA (5 mg/kg, i.p.) increased the survival of animals injected with a lethal dose of lipopolysaccharide. Thus adenosine receptor agonists may...Continue Reading

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Citations

Oct 7, 2004·European Journal of Pharmacology·Zdenĕk ZídekAntonín Holý
Apr 19, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Robert D LasleyRobert M Mentzer

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