Wang Xuewen, Li Guangping
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, China.
J Renin Angiotensin Aldosterone Syst. 2018 Jan-Mar;19(1):1470320318755269. doi: 10.1177/1470320318755269.
Activation of the renin-angiotensin system (RAS) plays an important role in atrial electrical remodeling (AER). The purpose of the present study was to evaluate the effects of irbesartan on cardiac sodium current (I) in a canine model of atrial fibrillation.
Eighteen dogs were randomized into sham, pacing or pacing+irbesartan groups ( n = 6 in each group). The dogs in the pacing and irbesartan group were paced at 500 bpm for two weeks. Irbesartan (60 mg·kg·d) was administered orally in the pacing+irbesartan groups. I was recorded using the whole-cell patch clamp technique from canine atrial myocytes. The expressions of cardiac Na channels (Nav1.5) mRNA were semi-quantified by reverse transcription-polymerase chain reaction.
Our results showed that I density and Nav1.5 mRNA expression in the pacing group decreased significantly ( p < 0.05 vs. sham). However, rapid atrial pacing had no effects on the half-activation voltage (V) and half-inactivation voltage (V) of I ( p > 0.05 vs. sham). Irbesartan significantly increased I densities and gene expression and hyperpolarized V without concomitant changes in V.
Irbesartan significantly increased I densities, which contributed to improving intra-atrial conduction and prevented the induction and promotion of AF in atrial pacing dogs.
肾素-血管紧张素系统（RAS）的激活在心房电重构（AER）中起重要作用。本研究旨在评估厄贝沙坦对犬心房颤动模型中心脏钠电流（I）的影响。
18只犬被随机分为假手术组、起搏组或起搏+厄贝沙坦组（每组n = 6）。起搏组和厄贝沙坦组的犬以500次/分钟的频率起搏两周。起搏+厄贝沙坦组口服厄贝沙坦（60mg·kg·d）。采用全细胞膜片钳技术记录犬心房肌细胞的I。通过逆转录-聚合酶链反应对心脏钠通道（Nav1.5）mRNA的表达进行半定量分析。
我们的结果显示，起搏组的I密度和Nav1.5 mRNA表达显著降低（与假手术组相比，p < 0.05）。然而，快速心房起搏对I的半激活电压（V）和半失活电压（V）没有影响（与假手术组相比，p > 0.05）。厄贝沙坦显著增加了I密度和基因表达，并使V超极化，而V没有随之改变。
厄贝沙坦显著增加了I密度，这有助于改善心房内传导，并预防心房起搏犬房颤的诱发和进展。
