Postconditioning Protects Against Reperfusion Injury in Hypertensive Dilated Cardiomyopathy by Activating MEK/ERK1/2 Signaling

BackgroundPostconditioning (PostC) cardioprotection has been related to up-regulation of survival kinases; however, the efficacy of PostC and the role of ERK1/2 (extracellular signal-regulated kinase 1/2) remain to be substantiated in hypertension states that may produce “pathologic remodeling.” Therefore, in this work we compared PostC effect and assessed the role of ERK1/2 activation in a model of hypertensive dilated cardiomyopathy (DCM), versus normal (Sham) and compensated hypertrophy (CH) models.Methods and ResultsRats were subjected to angiotensin II administration until development of cardiovascular diseases. Then, isolated hearts underwent ischemia followed by PostC and reperfusion. PostC maintained the double product in all groups. PostC reduced infarct size from 36.16 ± 3% to 9.8% ± 2.2 in Sham, from 37.5 ± 2.4% to 12 ± 3% in CH, and from 40 ± 2.4% to 11.55 ± 3% in DCM. Inhibition of the mitogen-activated protein kinase kinase (MEK)/ERK1/2 pathway had different effects on PostC-conferred cardioprotection in the evaluated groups. Interestingly, although phosphatidylinositol-3-kinase activation was negligible in PostC DCM hearts, we observed Akt activation.ConclusionsPostC confers cardioprotection through alternative survival pathways in normal and CH hearts, and cardiac function recovery in DCM relies mainly on MEK/ERK1/2 cascade. Down-regulation of phosphatidylinositide 3-kinase does not affect the cardioprotective response in DCM, because MEK/ERK1/2 cascade may convey direct Akt activation, strengthening downstream signaling.