依那普利、厄贝沙坦和血管紧张素（1-7）对快速心房起搏犬心房肌钠通道重构的干预作用  

Effects of enalapril,irbesartan and Ang（1-7） on sodium current remodeling in a canine model of rapid atrial pacing

作　　者：王学文[1] 李健[1] 徐昭[1] 杨万松[1] 李广平[1] 

机构地区：[1]天津医科大学第二医院心脏科、天津心脏病学研究所, 300211

出　　处：《中华心律失常学杂志》2011年第2期136-141,共6页Chinese Journal of Cardiac Arrhythmias

基　　金：国家自然科学基金（30770863）

摘　　要：目的观察依那普利、厄贝沙坦和血管紧张素（1-7）[Ang（1-7）]对快速心房起搏犬心房肌细胞钠通道电流（INa）的干预作用。方法普通杂种犬30只随机分为5组，每组6只。单纯心房起搏组（C组）、心房起搏＋依那普利组（EN组）、心房起搏＋厄贝沙坦组（IB组）和心房起搏＋Ang（1-7）组（A组）犬行心房快速起搏（500次／min）2周；假手术组（S组）不行起搏刺激。应用膜片钳技术检测心房肌细胞，INa电流密度及通道激活和失活特性。结果c组INa电流密度较s组明显降低（P〈0．05）；EN组、IB组和A组，INa电流密度较c组明显升高（P〈0．05）。与s组相比，起搏对INa的电压依赖性激活没有影响（P〉0．05）；与C组和s组相比，在EN组、IB组和A组，钠通道半激活电位更加超极化（P〈0．05）。与s组相比，快速心房起搏以及3种干预因素对INa的电压依赖性失活没有明显影响（P〉0．05）。结论依那普利、厄贝沙坦和Ang（1-7）通过加快INa的激活过程而增加心房肌INa电流幅度，有助于提高心房肌传导速度，从而抑制快速起搏所致的电重构。Objective To investigate the effects of angiotensin-converting enzyme inhibitor（ACEI） enalapril, angiotensin-receptor blocker （ARB） irbesartan and Angiotensin （ 1-7 ） [ （ Ang（ 1-7 ） ] on INa of the atrium induced by rapid atrial pacing in a canine model and to explore the mechanism and difference of therapeutic effects of the three agents on atrial fibrillation （AF）. Methods Thirty mongrel dogs were randomly divided into sham-operated group, paced, paced ＋ enalapril, paced ＋ irbesartan or paced ＋ Ang （ 1-7 ） group, 6 dogs in each group. The dogs in paced,paced ＋ enalapril ,paced ＋ irbesartan and paced ＋ Ang（1-7） group received rapid atrial pacing（RAP） at 500 beats per minutes for 2 weeks. The pacemakers in sham-operated group were instrumented without pacing. The dogs in paced ＋ enalapril,paced ＋ irbesartan received orally enalapril（2 mg · kg-1· d-1） or irbesartan（60 mg· kg-1· d-1）, respectively. The dogs in paced ＋ Ang-（1-7） group received Ang-（ 1-7 ） （6 p,g · kg-1 · h-1 ）intravenously during the pacing. The whole-cell patch-clamp technique was used to record left atrial IN. currents in right atrial tissue. Results The IN. densities were significantly reduced in atrial myocytes from paced dogs （ P 〈 0.05 vs. sham ）. Enalapril, irbesartan and Ang （ 1-7 ） increased INa densities compared with paced group（ P 〈 0. 05 ）. The voltage dependence of activation of INa was not altered in paced group compared with sham-operated group. Half-activation voltage（ Vl/2aot ）in enalapril, irbesartan and Ang（ 1-7 ）group was more negative versus sham-operated and paced group （ P 〈 0. 05, respectively）. Enalapril, irbesartan, Ang （1-7） and RAP had no effects on half-inactivation voltage （V1/2inact ）of INa. Conclusions Enalapril, irbesartan and Ang（ 1-7 ）increase INa densities, suppress AER and contribute to improve electrical impulses conduction velocity in chronic rapid atrial pacing dogs.

关 键 词：血管紧张素(1-7) 钠通道 心房电重构 肾素-血管紧张素系统 膜片钳技术 

分 类 号：R541.7[医药卫生—心血管疾病]