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

被引:7
作者
Yang, Yu [1 ]
Liu, Yongzheng [1 ]
Ma, Changhui [1 ]
Li, Ruiling [1 ]
Yang, Qian [1 ]
Zhang, Kai [1 ]
Cheng, Lijun [1 ]
Yuan, Meng [1 ]
Zhang, Yue [1 ]
Zhao, Zhiqiang [1 ]
Li, Guangping [1 ]
机构
[1] Tianjin Med Univ, Tianjin Inst Cardiol, Dept Cardiol, Tianjin Key Lab Ionic Mol Funct Cardiovasc Dis,Hos, Tianjin 300211, Peoples R China
基金
中国国家自然科学基金;
关键词
Atrial fibrillation; Atrial fibrosis; Atrial remodeling; Eplerenone; MINERALOCORTICOID RECEPTOR; FIBRILLATION;
D O I
10.1016/j.carpath.2022.107432
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Atrial fibrillation (AF) is closely associated with the overactivation of the renin-angiotensinaldosterone 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.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
引用
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页数:10
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