Mechanisms of the protective effects of urocortin on coronary endothelial function during ischemia–reperfusion in rat isolated hearts

1 Urocortin is a vasodilator peptide related to corticotrophin‐releasing factor, which may protect endothelial function during coronary ischemia–reperfusion (I–R). The aim of this study was to study the mechanisms of this protective effect. 2 Hearts from Sprague–Dawley rats were isolated and perfused at constant flow and then exposed to 15 min global zero‐flow ischemia, followed by 15 min reperfusion. The relaxation to acetylcholine (10 n M –10  μ M ) was recorded after pre‐constriction of the coronary vasculature with U46619 (100–300 n M ) in ischemic–reperfused or time‐control hearts. 3 After I–R, the coronary relaxation to acetylcholine was reduced and this reduction was attenuated by treatment with urocortin (10 p M ), administered before ischemia and during reperfusion. 4 This urocortin‐induced improvement of the relaxation to acetylcholine was not modified by tetraethylammonium (10 m M ), blocker of Ca 2+ dependent‐potassium channels; glibenclamide (10  μ M ), blocker of K ATP channels; N w ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 100  μ M ), blocker of nitric oxide synthesis; or meclofenamate (10  μ M ), blocker of cyclooxygenase, but it was abolished by chelerythrine (3  μ M ), blocker of protein kinase C (PKC). 5 These results suggest that urocortin may protect coronary endothelial function during I–R by activation of PKC.British Journal of Pharmacology (2005) 145 , 490–494. doi: 10.1038/sj.bjp.0706208