阿米洛利对大鼠压力超负荷性心肌肥厚的抑制作用

Effect of Amiloride on Cardiac Hypertrophy Induced by Partial Ligation of Abdominal Aorta in SD Rats

目的 观察钠氢交换体 (NHE)抑制剂阿米洛利 (Ami)对压力超负荷左室肥厚 (LVH)大鼠心功能、心肌细胞内游离钙浓度 ([Ca2 + ]i)及心肌细胞膜Na+ 、K+ ATP酶活性的影响。方法 ①同步记录离体工作心脏LVSP、LVEDP、±dp/dtmax及T值 ;②测定Fura 2 /A负载后的单个心室肌细胞的 [Ca2 + ]i;③光电比色法测定Na+ 、K+ ATP酶的活性。结果 ①与对照组相比 ,LVH组LVEDP和T值明显增加 ,-dp/dtmax明显降低 (均P <0 0 1) ;与LVH组相比 ,Ami组和Ena组的LVEDP及T值明显下降 (均P <0 0 1)。②与对照组相比 ,LVH组的心肌细胞 [Ca2 + ]i明显增高 ,细胞膜Na+ 、K+ ATP酶活性明显降低 (均P <0 0 1) ;Ami及Ena可降低LVH大鼠的 [Ca2 + ]i,升高其Na+ 、K+ ATP酶活性 (均P <0 0 1)。结论 压力超负荷大鼠心脏舒张功能明显下降 ,心室肌细胞 [Ca2 + ]i增高 ,心肌细胞膜Na+ 、K+ ATP酶活性受损 。

Objective To study the effects of amiloride and of enalapril on cardiac function as well as [Ca 2+ ] i and the myocardial membrane Na + ,K + ATPase activities from LVH rats induced by partial ligation of the abdominal aorta. Methods ① Cardiac function was assessed from LVSP, LVEDP, ±d p /d t max and T value recorded synchronously in the working heart. ② Using Fura 2/AM as fluorescent Ca 2+ indicator, the [Ca 2+ ] i was measured. ③ The Na + ,K + ATPase activity of myocardial membrane was measured. Results\ ①There was an increase in LVEDP and T value, and a diminution in d p /d t max , in LVH as compared with sham operated (control) rats ( P <0 01 for each). Amiloride and enalapril decreased the LVEDP and T value of LVH. Besides enalapril augmented d p /d t max .( P <0 01 respectively). ②Fura 2/AM loaded cardiac myocytes from LVH exhibited higher [Ca 2+ ] i and lower Na + ,K + ATPase activity of myocardial membrane fractions than those from control ( P <0 01), and these were prevented following treatment with either amiloride or enalapril. Conclusion ①We conclude that hearts from LVH exhibit diastolic dysfunction, despite relatively normal systolic function, and this can be ameliorated by both amiloride and enalapril. ②LVH ventricular myocytes display an increase in [Ca 2+ ] i and a decrese in myocardial membrane Na + ,K + ATPase activity, and again these abnormalities can be reversed by amiloride or enalapril.