Intermedin improves cardiac function and sympathetic neural remodeling in a rat model of post myocardial infarction heart failure

Xu,Bin; Xu,Hao; Cao,Heng; Liu,Xiaoxiao; Qin,Chunhuan; Zhao,Yanzhou; Han,Xiaolin; Li,Hongli

doi:10.3892/mmr.2017.6776

Intermedin improves cardiac function and sympathetic neural remodeling in a rat model of post myocardial infarction heart failure

Authors:
- Bin Xu
- Hao Xu
- Heng Cao
- Xiaoxiao Liu
- Chunhuan Qin
- Yanzhou Zhao
- Xiaolin Han
- Hongli Li
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Affiliations: Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
Published online on: June 14, 2017 https://doi.org/10.3892/mmr.2017.6776
Pages: 1723-1730
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging evidence has suggested that intermedin (IMD), a novel member of the calcitonin gene‑related peptide (CGRP) family, has a wide range of cardioprotective effects. The present study investigated the effects of long‑term administration of IMD on cardiac function and sympathetic neural remodeling in heart failure (HF) rats, and studied potential underlying mechanism. HF was induced in rats by myocardial infarction (MI). Male Sprague Dawley rats were randomly assigned to either saline or IMD (0.6 µg/kg/h) treatment groups for 4 weeks post‑MI. Another group of sham‑operated rats served as controls. Cardiac function was assessed by echocardiography, cardiac catheterization and plasma level of B‑type natriuretic peptide (BNP). Cardiac sympathetic neural remodeling was assessed by immunohistochemistical study of tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) immunoreactive nerve fibers. The protein expression levels of nerve growth factor (NGF), TH and GAP43 in the ventricular myocardium were studied by western blotting. Ventricular fibrillation threshold (VFT) was determined to evaluate the incidence of ventricular arrhythmia. Oxidative stress was assessed by detecting the activity of superoxide dismutase and the level of malondialdehyde. Compared with rats administrated with saline, IMD significantly improved cardiac function, decreased the plasma BNP level, attenuated sympathetic neural remodeling, increased VFT and suppressed oxidative stress. In conclusion, these results indicated that IMD prevents ventricle remodeling and improves the performance of a failing heart. In addition, IMD attenuated sympathetic neural remodeling and reduced the incidence of ventricular arrhythmia, which may contribute to its anti‑oxidative property. These results implicate IMD as a potential therapeutic agent for the treatment of HF.

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