# Eplerenone Inhibits Atrial Autonomic Nerve Remodeling in Atrial Fibrillation Through ERK1/2 MAPK Pathway

## TL;DR

Eplerenone reduces nerve changes in the heart that lead to atrial fibrillation by affecting a specific signaling pathway.

## Contribution

This study reveals a new mechanism by which eplerenone prevents atrial nerve remodeling through the ERK1/2 MAPK pathway.

## Key findings

- Eplerenone reduced the activation of the ERK1/2 MAPK pathway in AF models.
- Eplerenone inhibited the expression of nerve-related growth factors and reduced AF duration.
- Eplerenone modulated circulating neurohormones and prevented atrial nerve remodeling.

## Abstract

Atrial autonomic nerve system (ANS) remodeling plays an important role in atrial fibrillation (AF). Mineralocorticoid receptor antagonists (MRAs) have been proved to be effective in preventing atrial structural remodeling. However, the effects of MRA on ANS remodeling in AF and the underlying mechanisms are still unknown.

Methods: Then, 21 rabbits were randomized into sham, pacing, and pacing + eplerenone groups. To verify the effect of aldosterone on ANS remodeling, 18 SD rats were pumped with aldosterone. HL-1 cells were subjected to control treatment or rapid pacing with or without eplerenone or U0126 (an inhibitor of ERK1/2). Atrial sympathetic and parasympathetic remodeling was detected by immunohistochemical staining, Western blotting, and RT-PCR. The circulating neurohormone and atrial electrophysiology were also assessed.

Results: The ERK1/2 MAPK pathway was significantly activated in AF rabbit/HL-1 cell models, resulting in the upregulation of key downstream protein; this effect was significantly restored by eplerenone. Eplerenone prevented the alterations in circulating neurohormone, reduced the mRNA level of sympathetic and parasympathetic-related growth factors, and inhibited the inducibility and duration of AF.

Conclusions: Eplerenone inhibited atrial autonomic nerve remodeling and the occurrence of AF through modulating the ERK1/2 MAPK pathway.