Protective effects of aliskiren on atrial ionic remodeling in a canine model of rapid atrial pacing.
OBJECTIVE
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.
Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People's Republic of China.
Zhiqiang
Z
Zhao
Xinghua
X
Wang
Jian
J
Li
Wansong
W
Yang
Lijun
L
Cheng
Yan
Y
Chen
Tong
T
Liu
Enzhao
E
Liu
Kangyin
K
Chen
Guangping
G
Li
D000577:Amides / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects* / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics; D002304:Cardiac Pacing, Artificial / Q000379:methods; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005650:Fumarates / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006325:Heart Atria / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D012083:Renin / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000577:Amides; D020746:Calcium Channels, L-Type; D005650:Fumarates; C419385:L-type calcium channel alpha(1C); D062554:NAV1.5 Voltage-Gated Sodium Channel; D000804:Angiotensin II; C446481:aliskiren; D012083:Renin