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

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.

Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis

“…Contrary to this mechanism, it is a well‐investigated phenomenon that oxidative stress is increased and has a critical role in sympathetic neural remodelling (hyperinnervation) following MI and augments the expression of NGF in infarcted rat hearts 99 (more in paragraph 4.2). The inhibition of the superoxide generation decreased the expression of NGF and attenuated sympathetic neural remodelling following MI 109–111 …”

“…The inhibition of the superoxide generation decreased the expression of NGF and attenuated sympathetic neural remodelling following MI. [109][110][111] Autophagy Many studies have also suggested that autophagy plays an adaptive role in protecting cardiomyocytes after ischaemic injury and suppresses the acceleration of HF. 103,112 In a recent study, Wang et al 103 found that NGF improves myocardial ischaemia reperfusion injury in a mouse model and that the protective effect of NGF is associated with increased autophagy-mediated ubiquitination.…”

Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture

“…We observed that NET mRNA expression in myocardial tissue was lower in the M group than in the S group, but higher in the E group compared to the M group. GAP-43 is a neuronspeci c protein that plays an important role in axon outgrowth in neurons [35]. Following nerve injury GAP-43 is upregulated in regenerating axons, which is positively correlated with sympathetic excitability [31].However, this can aggravate myocardial injury.…”

Comparison between renal denervation and metoprolol on the susceptibility of ventricular arrhythmias in rats with myocardial infarction

“…Sympathetic nerve remodeling 6 , 7 refers to a series of pathophysiological changes after MI, including myocardial denervation, nerve sprouting, sympathetic over-regeneration and high domination, ultimately developing into electrophysiological heterogeneity. This may form the basis for increased susceptibility of VAs in rats with ischemic cardiomyopathy 8 .…”