Article date: June 2005
By: Angel Luis García‐Villalón, Yesika María Amezquita, Luis Monge, Nuria Fernández, Belén Climent, Ana Sánchez, Godofredo Diéguez in Volume 145, Issue 4, pages 490-494
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 Ca2+ dependent‐potassium channels; glibenclamide (10 μM), blocker of KATP channels; Nw‐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.
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 Ca2+ dependent‐potassium channels; glibenclamide (10 μM), blocker of KATP channels; Nw‐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.
British Journal of Pharmacology (2005) 145, 490–494. doi:10.1038/sj.bjp.0706208
DOI: 10.1038/sj.bjp.0706208
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