Cardioprotective action of urocortin in postconditioning involves recovery of intracellular calcium handling |
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Authors: | Calderón-Sánchez Eva María Ruiz-Hurtado Gema Smani Tarik Delgado Carmen Benitah Jean Pierre Gómez Ana María Ordóñez Antonio |
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Affiliation: | a Laboratorio de Fisiopatología Cardiovascular, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen de Rocío/CSIC/Universidad de Sevilla. 41013, Sevilla, Spain b Inserm, U637, Universités de Montpellier 1&2, Montpellier, France c Inserm, U769, Université Paris 11, Paris, France d Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain e Centro de Investigaciones Biológicas (CSIC) 28040 Madrid, Spain |
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Abstract: | Ischemia/reperfusion (I/R) damage in the heart occurs mainly during the first minutes of reperfusion. Urocortin (Ucn) is a member of the corticotrophin-releasing factor that has been identified as a potent endogenous cardioprotector peptide when used in pre- and postconditioning protocols. However, the underlying mechanisms are not completely elucidated. Here, we focused on intracellular calcium ([Ca2+]i) handling by Ucn when applied in early reperfusion. We used Langendorff-perfused rat hearts to determine hemodynamic parameters, and confocal microscopy to study global [Ca2+]i transients evoked by electrical stimulation in isolated cardiomyocytes loaded with fluorescence Ca2+ dye fluo-3AM. We found that the acute application of Ucn at the onset of reperfusion, in isolated hearts submitted to ischemia, fully recovered the hearts contractility and relaxation. In isolated cardiac myocytes, following ischemia we observed that the diastolic [Ca2+]i was increased, the systolic [Ca2+]i transients amplitude were depressed and sarcoplasmic reticulum (SR) Ca2+ load was reduced. These effects were correlated to a decrease in the Na+/Ca2+ exchanger (NCX) activity. Importantly, Ucn applied at reperfusion produced a complete recovery in diastolic [Ca2+]i and global [Ca2+]i transient amplitude, which were due to NCX activity improvement. In conclusion, we demonstrated that [Ca2+]i handling play an essential role in postconditioning action of Ucn. |
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Keywords: | Urocortin Ischemia/reperfusion Postconditioning Calcium handling |
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