Effects of adenosine receptor agonists on nitric oxide release in mouse during endotoxemia

The effects of adenosine receptor agonists on plasma NOx- (NO2- and NO3-) production in mice treated with lipopolysaccharide (LPS) were investigated. NOx- is the stable decomposition product of nitric oxide (NO), which can be measured as a marker of NO production. Injection of the mice with LPS resulted in increased plasma NOx- concentration, reaching a peak after 8 hr (38 times basal level) and then declining slowly. Pretreatment with the adenosine agonists R-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)carboxamidoadenosine (CPCA) and N6-cyclohexyladenosine (CHA) 1 hr before LPS administration caused a dose-dependent reduction of plasma NOx- concentration. The rank order of inhibitory potency was NECA > or = R-PIA > CPCA > CHA, which is characteristic of neither A1 nor A2 receptors.