Published in:
01-04-2014 | ORIGINAL ARTICLE
Protective Effects of Aliskiren on Atrial Ionic Remodeling in a Canine Model of Rapid Atrial Pacing
Published in: Cardiovascular Drugs and Therapy | Issue 2/2014
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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.