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Am J Physiol Heart Circ Physiol 284: H330-H336, 2003. First published September 19, 2002; doi:10.1152/ajpheart.01121.2001
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Vol. 284, Issue 1, H330-H336, January 2003

Cardioprotective action of CRF peptide urocortin against simulated ischemia in adult rat cardiomyocytes

Jennifer M. Gordon1,2, Gregory J. Dusting1, Owen L. Woodman2, and Rebecca H. Ritchie1

1 Howard Florey Institute and 2 Department of Pharmacology, University of Melbourne, Victoria 3010, Australia

The major objective of this study was to determine whether urocortin, a member of the corticotrophin-releasing factor (CRF) family, protects adult rat cardiomyocytes from ischemia that has been simulated by glucose deprivation and acidosis. When it was present during simulated ischemia, urocortin (0.1 µM) markedly attenuated the cellular injury, which was assessed by increases in creatine kinase and lactate dehydrogenase levels. This effect was comparable with that observed with adenosine (10 µM). The cardioprotective effect of urocortin was markedly attenuated by the protein kinase C inhibitor chelerythrine and by 5-hydroxydecanoate, an inhibitor of ATP-sensitive K+ channels. Cardiomyocytes were also protected from injury by pretreatment with urocortin, either by incubation for 5 min with a subsequent 10-min recovery or incubation for 20 min with a 20-h recovery before simulated ischemia. Similar cardioprotective effects were observed with ischemic preconditioning protocols during both immediate and delayed phases. In conclusion, in adult cardiomyocytes, urocortin has immediate and delayed cardioprotective actions that mimic ischemic preconditioning. These actions are mediated via protein kinase C and ATP-sensitive K+ channels.

adenosine; reperfusion; ischemic preconditioning; second window of protection


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