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Cardiovasc Res. 2007 Feb 1;73(3):488-96. Epub 2006 Nov 6.

Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts.

Author information

1
Department of Physiology, Pharmacology, Metabolism and Cardiovascular Sciences, Medical University of Ohio, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA.

Abstract

OBJECTIVE:

Because ouabain activates several pathways that are critical to cardioprotective mechanisms such as ischemic preconditioning, we tested if this digitalis compound could protect the heart against ischemia-reperfusion injury through activation of the Na+,K+-ATPase/c-Src receptor complex.

METHODS AND RESULTS:

In Langendorff-perfused rat hearts, a short (4 min) administration of ouabain 10 muM followed by an 8-minute washout before 30 min of global ischemia and reperfusion improved cardiac function, decreased lactate dehydrogenase release and reduced infarct size by 40%. Western blot analysis revealed that ouabain activated the cardioprotective phospholipase Cgamma1/protein kinase Cepsilon (PLC-gamma1/PKCepsilon) pathway. Pre-treatment of the hearts with the Src kinase family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2) blocked not only ouabain-induced activation of PLC-gamma1/PKCepsilon pathway, but also cardiac protection. This protection was also blocked by a PKCepsilon translocation inhibitor peptide (PKCepsilon TIP).

CONCLUSION:

Short exposure to a low concentration of ouabain protects the heart against ischemia/reperfusion injury. This effect of ouabain on the heart is most likely due to the activation of the Na+,K+-ATPase/c-Src receptor complex and subsequent stimulation of key mediators of preconditioning, namely PLC-gamma1 and PKCepsilon.

PMID:
17157283
PMCID:
PMC1852501
DOI:
10.1016/j.cardiores.2006.11.003
[Indexed for MEDLINE]
Free PMC Article

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