The protective role of adenosine in inducing nitric oxide synthesis in ratliver ischemia preconditioning is mediated by activation of adenosine A(2)receptors

This study aims to determine if the protective role of adenosine in liver i schemic preconditioning is mediated by the activation of adenosine receptor s and to ascertain which of these receptors is implicated in the process. A dministration of adenosine A(1) and A(2) receptor antagonists to preconditi oned animals indicates that hepatic preconditioning is mediated by the acti vation of adenosine A(2) receptors, Propentofylline tan inhibitor of adenos ine transport into cells) in the preconditioned group, subjected to previou s administration of an adenosine A(2) receptor antagonist, prevented the ne gative effect of the latter on the protection offered by preconditioning, A n increase of NO production was detected just immediately after hepatic pre conditioning, and the administration of an adenosine A(2) receptor antagoni st to the preconditioning group prevented this increase, thus abolishing th e protective effect of preconditioning, However, the administration of a NO donor to the preconditioned group subjected to previous administration of the adenosine A(2) receptor antagonist was able to maintain the preconditio ning effects. In conclusion, these results indicate that, in preconditionin g, the protective effect of adenosine could be a result of an increase in e xtracellular adenosine, This in turn would induce the activation of adenosi ne A(2) receptors, which, by eliciting an increase in NO generation, would protect against the injury associated with hepatic ischemia-reperfusion.