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Protective Effects of Aliskiren on Atrial Ionic Remodeling in a Canine Model of Rapid Atrial Pacing

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Abstract

Purpose

Aliskiren inhibits the activation of the renin-angiotensin system. Here, we investigated the effects of aliskiren on chronic atrial iron remodeling in the experimental canine model of rapid atrial pacing.

Methods

Twenty-eight dogs were assigned to sham (S), control paced (C), paced + aliskiren (10 mg Kg−1 d−1, A1), and paced + aliskiren (20 mg Kg−1 d−1, A2) groups. Rapid atrial pacing at 500 bpm was maintained for 2 weeks, while group S was not paced. Levels of serum angiotensin-converting enzyme and angiotensin II after pacing were determined by ELISA. Whole-cell patch-clamp technique, western blot, and RT-PCR were applied to assess atrial ionic remodeling.

Results

The density of I CaL and I Na currents (pA/pF) was significantly lower in group C compared with group S (I CaL: −4.09 ± 1.46 vs. −6.12 ± 0.58,P < 0.05; I Na: 30.48 ± 6.08 vs. 46.31 ± 4.73, P < 0.05). However, the high dose of aliskiren elevated the density of I CaL and I Na currents compared with group C (I CaL: −6.23 ± 1.35 vs. −4.09 ± 1.46, P < 0.05; I Na: 58.62 ± 16.17 vs. 30.48 ± 6.08, P < 0.01). The relative mRNA and protein expression levels of Cav1.2 and Nav1.5α were downregulated in group C respectively (Cav1.2: 0.46 ± 0.08; Nav1.5α: 0.52 ± 0.08, P < 0.01; Cav1.2: 0.31 ± 0.03; Nav1.5α: 0.41 ± 0.04, P < 0.01;), but were upregulated by aliskiren.

Conclusions

Aliskiren has protective effects on atrial tachycardia-induced atrial ionic remodeling.

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Acknowledgments

This work was supported by the Program of Natural Science Foundation of China (No. 81370300) and China Education Ministry Colleges and Universities Special Scientific Research Foundation for Doctoral Advisor Class (No. 20121202110004).

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Authors and Affiliations

  1. Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China

    Zhiqiang Zhao, Xinghua Wang, Jian Li, Wansong Yang, Lijun Cheng, Yan Chen, Tong Liu, Enzhao Liu, Kangyin Chen & Guangping Li

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  1. Zhiqiang Zhao
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Correspondence to Guangping Li.

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Zhao, Z., Wang, X., Li, J. et al. Protective Effects of Aliskiren on Atrial Ionic Remodeling in a Canine Model of Rapid Atrial Pacing. Cardiovasc Drugs Ther 28, 137–143 (2014). https://doi.org/10.1007/s10557-014-6509-x

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