Improving effects of eplerenone on atrial remodeling induced by chronic intermittent hypoxia in rats

Cardiovasc Pathol. 2022 Sep-Oct:60:107432. doi: 10.1016/j.carpath.2022.107432. Epub 2022 May 11.

Abstract

Objective: Atrial fibrillation (AF) is closely associated with the overactivation of the renin-angiotensin-aldosterone system. Large cohort studies and recent meta-analyses have shown that the utilization of mineralocorticoid receptor antagonists has positive effects on the prevention and development of AF. This study aimed to investigate the effects of eplerenone on atrial remodeling in AF model rats and elucidate its intrinsic mechanism.

Methods: Ninety male Sprague-Dawley rats were randomly divided into the control group, chronic intermittent hypoxia (CIH) group, and CIH-eplerenone intervention (CIH-E) group. Rats in the CIH and CIH-E groups received CIH for 6 weeks, and rats in the CIH-E group were additionally administered eplerenone gavage (10 mg/kg/d). After modeling, the baseline parameters of each group were examined. Histopathology, molecular biology, isolated electrophysiology, and patch clamp experiments were performed after sampling.

Results: Compared with the control group, rats in the CIH group showed atrial enlargement, significant aggravated fibrosis, upregulated JAK/STAT3 pathway, shortened effective refractory period (ERP), increased AF inducibility, and decreased peak current density of characteristic voltage-gated ion channels in atrial myocytes. After eplerenone intervention, rats in the CIH-E group had a smaller atrial diameter than those in the CIH group. Furthermore, downregulated JAK/STAT3 pathway, prolonged ERP, decreased AF inducibility, and increased peak current density of characteristic ion channels were also observed in the CIH-E group.

Conclusions: CIH induced significant atrial remodeling in rats and eplerenone significantly ameliorated the atrial remodeling caused by CIH. This could be attributed to the downregulation of the JAK/STAT3 pathway and the increase in the characteristic ion current density of atrial myocytes.

Keywords: Atrial fibrillation; Atrial fibrosis; Atrial remodeling; Eplerenone.

MeSH terms

  • Animals
  • Atrial Fibrillation* / etiology
  • Atrial Remodeling* / physiology
  • Eplerenone / pharmacology
  • Humans
  • Hypoxia / metabolism
  • Ion Channels
  • Male
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Ion Channels
  • Mineralocorticoid Receptor Antagonists
  • Eplerenone