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.
Drug Des Devel Ther. 2020 Sep 16;14:3755-3764. doi: 10.2147/DDDT.S262922. eCollection 2020.
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.
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.
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; <0.05). Compared with the control group, the densites of the calcium current ( ) and sodium current ( ) were reduced significantly in the CIH group ( : -3.16±0.61 pA/pF vs -7.13±1.98 pA/pF; : -50.97±8.71 pA/pF vs -132.58±25.34 pA/pF, respectively; all <0.05). Following intervention with aliskiren, the reductions in and were significantly improved, and the ionic modeling changes assessed at the mRNA and protein levels were also significantly improved.
CIH could alter atrial modeling and subsequently promote the occurrence and development of AF, which could be attenuated by treatment with aliskiren.
心房重构参与了心房颤动（房颤）的发病机制。阿利克仑作为一种直接肾素抑制剂，已被证明对心律失常具有保护作用。本研究旨在探讨阿利克仑在慢性间歇性低氧（CIH）大鼠模型中心房重构中的潜在作用。
将 45 只 Sprague-Dawley 大鼠随机分为三组（每组 15 只）：对照组；CIH 组；和 CIH 加阿利克仑（CIH-A）组。CIH 组和 CIH-A 组大鼠每天接受 6 小时 CIH，共 4 周。采用 Masson 三色染色评估心房纤维化。在分离的灌注心脏中进行电生理测试，以评估心房有效不应期和房颤的可诱导性。采用全细胞膜片钳技术测量心房离子重构，并用 Western blot 和实时定量聚合酶链反应评估离子通道的变化。
CIH 诱导明显的胶原沉积，阿利克仑显著减轻异常纤维化。与对照组和 CIH-A 组相比，CIH 组的房颤诱导率显著增加（分别为 23±24.5%、2.0±4.2%和 5.0±7.0%；<0.05）。与对照组相比，CIH 组钙电流（）和钠电流（）密度明显降低（：-3.16±0.61 pA/pF 比-7.13±1.98 pA/pF；：-50.97±8.71 pA/pF 比-132.58±25.34 pA/pF；均<0.05）。阿利克仑干预后，降低的 和 得到显著改善，mRNA 和蛋白水平评估的离子建模变化也得到显著改善。
CIH 可改变心房建模，进而促进房颤的发生和发展，阿利克仑治疗可减轻这种影响。
