Effects of Angiotensin Receptor Neprilysin Inhibitors on Inducibility of Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

Int Heart J. 2019 Sep 27;60(5):1168-1175. doi: 10.1536/ihj.19-065. Epub 2019 Sep 4.

Abstract

The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.

Keywords: Cardiac fibrosis; Connexin43; Myocardial infarction; Sympathetic nerve remodeling.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biopsy, Needle
  • China
  • Connexin 43 / metabolism*
  • Disease Models, Animal
  • Echocardiography / methods
  • Immunohistochemistry
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Neprilysin / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Risk Factors
  • Survival Rate
  • Sympathetic Nervous System / drug effects
  • Tachycardia, Ventricular / diagnostic imaging
  • Tachycardia, Ventricular / drug therapy*
  • Ventricular Remodeling / drug effects*

Substances

  • Connexin 43
  • Neprilysin