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

Abstract

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. 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 nM-10 μM) was recorded after pre-constriction of the coronary vasculature with U46619 (100-300 nM) in ischemic-reperfused or time-control hearts. After I-R, the coronary relaxation to acetylcholine was reduced and this reduction was attenuated by treatment with urocortin (10 pM), administered before ischemia and during reperfusion. This urocortin-induced improvement of the relaxation to acetylcholine was not modified by tetraethylammonium (10 mM), blocker of Ca 2+ dependent-potassium channels; glibenclamide (10 μM), blocker of K ATP channels; N w-nitro-L-arginine methyl ester (L-NAME, 100 μM), blocker of nitric oxide synthesis; or meclofenamate (10 μM), blocker of cyclooxygenase, but it was abolished by chelerythrine (3 μM), blocker of protein kinase C (PKC). These results suggest that urocortin may protect coronary endothelial function during I-R by activation of PKC. © 2005 Nature Publishing Group. All rights reserved.