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 induce d injury has been evaluated in this study. Thus hepatic ischemia-reper fusion or preconditioning plus ischemia-reperfusion was induced in rat s and the effect of nitric oxide administration or inhibition with add ition of the endothelin antagonist Bosentan was evaluated. Results sho w that the increases in plasma GPT release after ischemia-reperfusion were prevented after preconditioning. Inhibition of nitric oxide aboli shed the effect of preconditioning, addition of the endothelin antagon ist abolished the injurious effect of NO inhibition. Also, increased s ynthesis of endothelin has been detected after ischemia-reperfusion. a nd addition of NO or preconditioning prevented this increase, suggesti ng that increases of NO inhibit endothelin synthesis. Altogether this indicates that hepatic preconditioning is mediated by the inhibitory a ction of nitric oxide on endothelin levels. (C) 1996 Academic Press, I nc.