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Am J Physiol Heart Circ Physiol (September 19, 2002). doi:10.1152/ajpheart.01121.2001
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Articles in PresS, published online ahead of print September 19, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.01121.2001
Submitted on December 27, 2001
Accepted on September 6, 2002

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

Jennifer M. Gordon1, Gregory J. Dusting2, Owen L. Woodman3, and Rebecca H. Ritchie2*

1 Howard Florey Institute, Melbourne, Victoria, Australia; Department of Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia
2 Howard Florey Institute, Melbourne, Victoria, Australia
3 Department of Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia

* To whom correspondence should be addressed. E-mail: r.ritchie{at}hfi.unimelb.edu.au.

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 simulated by glucose deprivation and acidosis. Urocortin (0.1 µM) markedly attenuated the marked cellular injury (assessed by increases in creatine kinase and lactate dehydrogenase levels) when present during simulated ischemia. 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 potassium channels. Cardiomyocytes were also protected from injury by pretreatment with urocortin, either by incubation for 5 min with 10 min recovery, or for 20 min with 20 h recovery, prior to 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 potassium channels.




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