title: Cardioprotective action of urocortin in postconditioning involves recovery of intracellular calcium handling.
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 ([Ca(2+)](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 [Ca(2+)](i) transients evoked by electrical stimulation in isolated cardiomyocytes loaded with fluorescence Ca(2+) 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 [Ca(2+)](i) was increased, the systolic [Ca(2+)](i) transients amplitude were depressed and sarcoplasmic reticulum (SR) Ca(2+) load was reduced. These effects were correlated to a decrease in the Na(+)/Ca(2+) exchanger (NCX) activity. Importantly, Ucn applied at reperfusion produced a complete recovery in diastolic [Ca(2+)](i) and global [Ca(2+)](i) transient amplitude, which were due to NCX activity improvement. In conclusion, we demonstrated that [Ca(2+)](i) handling play an essential role in postconditioning action of Ucn.
authors.affiliation: Laboratorio de Fisiopatología Cardiovascular, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen de Rocío/CSIC/Universidad de Sevilla. 41013, Sevilla, Spain.
authors.forename: Eva María
authors.initials: EM
authors.lastname: Calderón-Sánchez
authors.forename: Gema
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.forename: Tarik
authors.initials: T
authors.lastname: Smani
authors.forename: Carmen
authors.initials: C
authors.lastname: Delgado
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Benitah
authors.forename: Ana María
authors.initials: AM
authors.lastname: Gómez
authors.forename: Antonio
authors.initials: A
authors.lastname: Ordóñez
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005456:Fluorescent Dyes / Q000737:chemistry; D006439:Hemodynamics; D057775:Ischemic Postconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D054832:Urocortins / Q000627:therapeutic use*; D014966:Xanthenes / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D002316:Cardiotonic Agents; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D054832:Urocortins; D014966:Xanthenes; C059715:Fluo-3; D002118:Calcium