Abstract
Introduction. Due to neuropathy in diabetic patients, the dysfunction of the autonomic nervous system occurs, and cardiac activity undergone excess sympathetic stimulation which is named cardiac autonomic neuropathy. Patients with cardiac autonomic neuropathy are at higher risk of left ventricular hypertrophy and are predisposed to cardiovascular events. It was established that metformin, a first-line agent for the initial pharmacotherapy of type 2 diabetes mellitus, poses significant cardioprotective effects. Nevertheless, its activity in the myocardium, subjecting the increased sympathetic tone, remains poorly investigated.
 The aim of the study – to explore the effects of metformin on cardiac remodeling after prolonged isoproterenol administration at a low dose.
 Research Methods. To induce cardiomyopathy, Wistar rats were injected intraperitoneally with isoproterenol (Iso – 5 mg/kg) in the continuous presence of metformin (М – 100 mg/kg) or vehicle only for 7 consecutive days. Tissue samples were stained with Hematoxylin&Eosin using standard method. The serum level of brain natriuretic peptide was estimated using the Rat BNP ELISA Kit. Statistical comparison of multiple groups was performed by one-way ANOVA followed by Bonferroni Test using GraphPad Prism version 5.00.
 Results and Discussion. The results of investigation demonstrate that metformin treatment significantly abolished cardiac hypertrophy in rats induced by isoproterenol administration at the daily dose 5 mg/kg for 7 days. Antihypertrophic effect of the drug was confirmed by its ability to diminish the serum level of brain natriuretic peptide. Structural fibrotic reorganization was prevented as well.
 Conclusions. Metformin exerts cardioprotection after prolonged isoproterenol administration at a low dose preventing hypertrophic and fibrotic remodeling and fetal genes reprogramming. Thus, it might be a potential tool in the prevention of cardiac remodeling in patients with sympathetic overactivity.
Highlights
Due to neuropathy in diabetic patients, the dysfunction of the autonomic nervous system occurs, and cardiac activity undergone excess sympathetic stimulation which is named cardiac autonomic neuropathy
The results of investigation demonstrate that metformin treatment significantly aboli shed cardiac hypertrophy in rats induced by isoproterenol administration at the daily dose 5 mg/kg for 7 days
First of all the effect of metformin on cardiac hypertrophy was investigated in rats induced by isoproterenol administration for 7 days
Summary
Due to neuropathy in diabetic patients, the dysfunction of the autonomic nervous system occurs, and cardiac activity undergone excess sympathetic stimulation which is named cardiac autonomic neuropathy. Patients with cardiac autonomic neuropathy are at higher risk of left ventricular hypertrophy and are predisposed to cardiovascular events. CAN is caused by damage of the autonomic nerve fibers that innervate the heart and blood vessels and leads to abnormalities in cardiovascular dynamics [3]. The first feature of diabetic CAN is usually vagus nerve damage Since this nerve is responsible for nearly 75 % of parasympathetic activity, alteration in its function causes resting tachycardia, since sympathetic influences become predominant [6]. After about five years increased heart rate even tually diminishes due to progressive sympathetic nerve fiber damage, it remains higher than in the healthy patients [1]. Declines in parasympathetic tone occur at night and CAN subjects expe rience more frequent left ventricular hypertrophy and are predisposed to cardiovascular events [7]. Searching for new therapeutic strategies, which can modulate adverse cardiac remodeling and prevent heart failure, is an urgent matter
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