High‑dose fasudil preconditioning and postconditioning attenuate myocardial ischemia‑reperfusion injury in hypercholesterolemic rats

Wu,Nan; Zhang,Xiaowen; Jia,Dalin

doi:10.3892/mmr.2013.1818

High‑dose fasudil preconditioning and postconditioning attenuate myocardial ischemia‑reperfusion injury in hypercholesterolemic rats

Authors:
- Nan Wu
- Xiaowen Zhang
- Dalin Jia
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Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Medical Genetics, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: November 20, 2013 https://doi.org/10.3892/mmr.2013.1818
Pages: 560-566

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Abstract

Fasudil may induce preconditioning and postconditioning against myocardial ischemia‑reperfusion injury in normal rats, however, their effectivenesses in hypercholesterolemia remains to be determined. The study aimed to investigate whether fasudil induces preconditioning and postconditioning in hypercholesterolemic rats and to determine the roles of the phosphoinositol 3‑kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) pathway and mitochondrial KATP (m‑KATP) channels in this process. Isolated rat hearts underwent 30 min global ischemia and 120 min reperfusion. Low‑ (1 mg/kg) or high‑dose (10 mg/kg) fasudil was administered 15 min prior to ischemia and at the initial onset of reperfusion. 5‑Hydroxydecanoic acid (5HD), an m‑KATP channel blocker, at 10 mg/kg was administered 5 min prior to reperfusion. Myocardial infarct size was estimated by 2,3,5‑triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase‑MB (CK‑MB) were analyzed from coronary effluents. Phosphorylation of Akt and eNOS was measured by immunoblotting. High‑dose fasudil‑induced preconditioning and postconditioning significantly reduced infarct size and the release of LDH and CK‑MB and increased the phosphorylation of Akt and eNOS compared with the control group, whereas low‑dose fasudil did not exert these beneficial effects. In addition, the cardioprotection of high‑dose fasudil‑induced preconditioning and postconditioning are blocked by 5HD. Low‑dose fasudil‑induced preconditioning and postconditioning are abrogated by hypercholesterolemia, while high‑dose fasudil restores the cardioprotection, which is involved in upregulation of the PI3K/Akt/eNOS pathway and inducing the opening of the m‑KATP channel.

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