Myocardial ischemia-reperfusion injury occurs in a wide spectrum of patients and represents a major public health problem. Despite the considerable progress that has been made in the field of myocardial protection, high-risk subsets of patients continue to exhibit ischemia-reperfusion-related complications. Recently Urocortin (Ucn) has been proposed as a new cardioprotector against chronic ischemia. We used Langendorff system to examine the effect of Ucn (10nM) in isolated rat heart under acute ischemia/reperfusion. We compared the contractility (dP/dt) in heart submitted to ischemia (30 min) and reperfusion (2 hours), and in hearts that were treated before ischemia with Ucn alone or in presence of glibenclamide (KATP inhibitor), H89 (PKA inhibitor) or GF109203X (PKC blocker). We observed that Ucn provoke an increase of heart contractility (=11%), decreased the left ventricular pressure (LVDP=52%) and decreased the pressure of coronary perfusion (PPC=14%). We found that Ucn induced a significant recovery of heart contractility after ischemia-reperfusion (92±11% vs 47±8% in the ischemic group). Furthermore, pre-treatment of hearts with glibenclamide to inhibit KATP channels prevented Ucn effects (dP/dt=54±10 % vs 92±11% in hearts treated with Ucn alone). However, Ucn effect was not sensitive to PKA inhibitor (H89, dP/dt=91±6%), neither to PKC blocker (GF109203X, dP/dt=89±5%). We conclude that Ucn induced heart protection against acute ischemia-reperfusion injury by KATP activation and seems not to involve the PKA and PKC pathway that was implicated in the later heart protection against apoptosis.

Acknowledgements: Ramon y Cajal, FIS (RECAVA, PI050396, PI052106), Consejería de Salud, 0182/2005 and 174/2006