AIM:Stress-activated signaling pathways responsiblefor hepatic ischemia reperfusion injury and theirmodulation by protective interventions are widelyunknown.Preconditioning of rat livers with AtrialNatriuretic Peptide(ANP)attenuates ischemiareperfusion injury(Gerbes et al.Hepatology 1998,28:1309-1317).Since ANP has recently been shown to bea regulator of the p38 MAPK pathway in endothelialcells(Kiemer et al.Circ Res 2002,90:874-881),aim ofthis study was to investigate activities of MAPK duringischemia and reperfusion and effects of ANP on MAPK.METHODS:Rat livers were perfused with KH-buffer inthe presence or absence of ANP for 20 min,kept in coldUW solution for 24 h,and reperfused for up to 120 min.Activities of p38 MAPK and JNK was determined by invitro phosphorylation assays using MBP and c-jun assubstrates.After SDS/PAGE electrophoresis,gels werequantified by phosphorimaging.RESULTS:Activity of p38 MAPK in control organsdecreased in the course of ischemia and reperfusionby 85%,whereas ANP increased p38 activity by up to30-fold.JNK activation of control livers increased in thecourse of ischemia and reperfusion by up to three-fold.This increase in JNK activity was slightly elevated inANP preconditioned organs.CONCLUSION:This work represents a systematicinvestigation of MAPK activation during liver ischemiaand reperfusion.Employing ANP,for the first time apharmacological approach to modulate these centralsignal transduction molecules is presented. AIM: Stress-activated signaling pathways responsible for hepatic ischemia reperfusion injury and their modulation by protective interventions are widelyunknown. Preconditioning of rat livers with Atrial Natriuretic Peptide (ANP) attenuates ischemiareperfusion injury (Gerbes et al. Hepatology 1998, 28: 1309-1317) has recently been shown to bea regulator of the p38 MAPK pathway in endothelial cells (Kiemer et al. Circ Res 2002, 90: 874-881), aim of study was to investigate activities of MAPK during ischemia and reperfusion and effects of ANP on MAPK. METHODS : Rat livers were perfused with KH-buffer inthe presence or absence of ANP for 20 min, kept in cold UW solution for 24 h, and reperfused for up to 120 min. Activations of p38 MAPK and JNK was determined by invitro phosphorylation assays using MBP and c-jun assubstrates. After SDS / PAGE electrophoresis, gels were quantified by phosphorimaging .RESULTS: Activity of p38 MAPK in control organsdecreased in the course of ischemia and reperfusionby 85%, where as ANP increased p38 activity by up to 30-fold. JNK activation of control livers increased in the course of ischemia and reperfusion by up to three-fold. His increase in JNK activity was slightly elevated in ANP preconditioned organs. CONCLUSION: This work represents a systematic investigation of MAPK activation during liver ischemia and reperfusion. Imperative ANP, for the first time apharmacological approach to modulate these central signaling transducers molecules is presented.