Aim: 

Urocortin is a neuropeptide belonging to the "corticotropin releasing factors" family, which has been described to modulate heart performance. The aim of this study is to evaluate the positive inotropic effect of urocortin in ex vivo perfused rat hearts and to characterize its signalling pathway.

Methods: 

Ex vivo perfused Wistar rat heart was studied by a Langendorff system to evaluate the hemodynamics parameters under different treatments. Moreover, we used standard whole-cell patch clamp recording to evaluate L-type Ca²⁺ channel activity in isolated cardiomyocytes treated with urocortin.

Results: 

The application of urocortin in ex vivo Langendorff perfused Wistar rat heart induced a dose dependent enhancement of heart contractility (EC50= 8 nM). Urocortin increased progressively the maximal derivative of left ventricular pressure (+dP/dt) independently of protein kinase A activation. Urocortin-induced positive inotropic effect involved the activation of protein kinase C and mitogen activated protein kinase proteins. Moreover, using standard whole cell patch-clamp recording and Ca²⁺ imaging techniques, we found that Urocortin increased the intracellular Ca²⁺ concentration and enhanced the L-type Ca²⁺ current density in Urocortin-treated cardiomyocytes independently of protein kinase A activation.

Conclusion: 

This study shows that urocortin has an inotropic positive effect in rat hearts, which involves protein kinase C and mitogen activated protein kinase pathway; and L-type Ca²⁺ currents increase.

Acknowledgments: 

This study was supported by "Red Cardiovascular RECAVA" of "Instituto Carlos III" [grant number: RD06-0014-0020, RD06-0014-0007]; and "Consejería de Innovación y Ciencias de la Junta de Andalucía" [grant numbers: P06-CTS-01711]. T.S is a "Ramon y Cajal" Researcher and E.C. is a fellow of RECAVA.