Metformin Exerts Cardioprotection in Isoproterenol-Induced Cardiomyopathy in Rats

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.