Liver ischemic preconditioning is mediated by the inhibitory action of nitric oxide on endothelin

The concerted involvement of both NO and endothelin in the protective effect of preconditioning against hepatic ischemia-reperfusion induced injury has been evaluated in this study. Thus hepatic ischemia-reperfusion or preconditioning plus ischemia-reperfusion was induced in rats and the effect of nitric oxide administration or inhibition with addition of the endothelin antagonist Bosentan was evaluated. Results show that the increases in plasma GPT release after ischemia-reperfusion were prevented after preconditioning. Inhibition of nitric oxide abolished the effect of preconditioning, addition of the endothelin antagonist abolished the injurious effect of NO inhibition. Also, increased synthesis of endothelin has been detected after ischemia-reperfusion, and addition of NO or preconditioning prevented this increase, suggesting that increases of NO inhibit endothelin synthesis. Altogether this indicates that hepatic preconditioning is mediated by the inhibitory action of nitric oxide on endothelin levels.