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.