慢性房颤犬心房肌肾素血管紧张素系统激活的影响及卡托普利的干预作用

Effects of Captopril on the activation of atrial renin angiotensin system in the chronic atrial fibrillation dogs

目的探讨慢性房颤实验犬心房肌肾素血管紧张素系统(RAS)的影响及卡托普利的干预作用。方法健康杂种犬26只,随机分为三组：对照组(n=6),起搏组(n=11),治疗组(n=9)。起搏组和治疗组安置埋藏式高频率心脏起搏器(400次/min),快速起搏犬右心耳8周,治疗组于起搏前3 d至起搏后第8周每日口服卡托普利50 mg,每天两次。起搏8周后,两组分别处死动物,于左右心房、心耳及房间隔取材,测定心房组织血管紧张素Ⅱ(AngⅡ)含量及心房肌细胞内Ca^(2+)浓度。对照组未安置起搏器,与起搏、治疗组同步行相应检查。结果起搏8周后,起搏组、治疗组和对照组测得心房组织AngⅡ含量分别为(29．83±5．73)pg/ml,(13．23±3．15)pg/ml,(11．38±2．14)pg/ml。与对照组比较,起搏组AngⅡ含量明显增高(P＜0．01),而治疗组与对照组比较,差异无显著性(P＞0．05)。三组测得心房肌细胞内Ca^(2+)浓度分别为(35．32±4．88)μg/mg,(25．44±4．19)μg/mg,(24．06±3．51)μg/mg。与对照组比较,起搏组明显升高(P＜0．01),而治疗组没有(P＞0．05)。结论长期快速起搏实验犬心房组织AngⅡ含量增高、心房肌细胞内钙超载。卡托普利可阻滞慢性房颤实验犬心房组织RAS激活,阻止细胞内钙超载,从而消除房颤形成的基质。

Objective To investigate the activation of renin angiotensin system （RAS） in the chronic atrial fibrillation （AF） dogs and the effects of Captopril in the treatment of AF. Methods Twenty - six mongrel dogs were randomly divided into three groups： pacing group （ n = 11）, treatment group （ n = 9） and control group （ n = 6） . High frequency pacing （400 b/min） of the right atrial appendage was performed for 8 weeks in the pacing group and treatment group with permanent pacemaker. Pacing was not performed in the control group. In the treatment group, the dogs were given Captopril orally 50 mg twice a day from 3 days before pacing to 8 weeks after pacing. Tissue samples were obtained from the atrial appendages and both the left and right atria when dogs were killed. The level of angiotensin Ⅱ （ Ang Ⅱ ） and the intracellular Ca^2＋ concentrations were assayed by radio - immunity and spectrocomparator. Results The atrial Ang Ⅱ concentrations were （29.83 ＋ 5.73） pg/ml, （13.23 ＋ 3.15） pg/ml, （ 11.38 ＋ 2.14） pg/ml in pacing, treatment and control group, respectively. Compared with control group, the atrial Ang Ⅱ concentrations in pacing group were significantly increased （ P 〈 0.01 ）, but no significant differences were found between treatment group and control group （P 〉 0.05 ）. The intracellular Ca^2＋ concentrations were （35.32 ± 4.88） μg/mg, （ 25.44 ± 4. 19） μg/mg, （ 24.06 ± 3.51 ） μg/mg in pacing, treatment and control group, respectively. Intracellular Ca^2＋ concentrations were higher in pacing group than that in the other two groups （P 〈 0.01 ） . But in treatment group, the intracellular Ca^2＋ concentrations were almost the same as that in the control group （ P 〉 0. 05 ） . Conclusion Chronic high frequency pacing could significantly increase the level of the atr±ial Ang Ⅱ and intracellular Ca^2＋ concentrations. Captopril could inhibit the RAS activation and the intracellular calcium overload and might present a new component for the treatment of AF.