Drug Design, Development and Therapy (Sep 2020)
The Potential Effects of Aliskiren on Atrial Remodeling Induced by Chronic Intermittent Hypoxia in Rats
Abstract
Shuai Miao,* Yu Yang,* Ruiling Li, Li Yin, Kai Zhang, Lijun Cheng, Xiaona Xu, Weiding Wang, Zhiqiang Zhao, Guangping Li Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiqiang Zhao; Guangping LiTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People’s Republic of ChinaTel +86-22-88328368Fax +86-22-28261158Email [email protected]; [email protected]: Atrial remodeling takes part in the pathogenesis of atrial fibrillation (AF). Aliskiren, as a direct renin inhibitor, has been shown to exert protective effects against arrhythmia. The aim of this study was to investigate the potential role of aliskiren in atrial remodeling in a chronic intermittent hypoxia (CIH) rat model.Methods: A total of 45 Sprague–Dawley rats were randomly assigned into three groups (n=15 per group): control group; CIH group; and CIH with aliskiren (CIH-A) group. CIH and CIH-A rats were subjected to CIH for 6 h per day for 4 weeks. Atrial fibrosis was evaluated using Masson’s trichrome staining. Electrophysiological tests were conducted in the isolated perfused hearts to assess the atrial effective refractory period and inducibility of AF. Atrial ionic remodeling was measured using the whole-cell patch-clamp technique, and Western blotting and real-time quantitative polymerase chain reactionwere performed to evaluate changes in ion channels.Results: CIH induced obvious collagen deposition, and the abnormal fibrosis was significantly attenuated by aliskiren. The inducibility of AF was increased significantly in the CIH group compared with the control and CIH-A groups (23± 24.5% vs 2.0± 4.2% vs 5.0± 7.0%, respectively; P< 0.05). Compared with the control group, the densites of the calcium current (ICaL) and sodium current (INa) were reduced significantly in the CIH group (ICaL: − 3.16± 0.61 pA/pF vs − 7.13± 1.98 pA/pF; INa: − 50.97± 8.71 pA/pF vs − 132.58± 25.34 pA/pF, respectively; all P< 0.05). Following intervention with aliskiren, the reductions in ICaL and INa were significantly improved, and the ionic modeling changes assessed at the mRNA and protein levels were also significantly improved.Conclusion: CIH could alter atrial modeling and subsequently promote the occurrence and development of AF, which could be attenuated by treatment with aliskiren.Keywords: atrial fibrillation, aliskiren, chronic intermittent hypoxia, atrial remodeling
