钙拮抗剂对高血压大鼠心房肌L-型钙通道和钠-钙离子交换器mRNA的影响

Influences of Ca^(2+) antagonist on the mRNA levels of L-type Ca_(2+) channel and Na^+ -Ca^(2+) exchanger in the atria of hypertensive rats

目的:观察钙拮抗剂地尔硫(艹卓)对Goldblatt高血压大鼠模型心房肌L-型钙通道α_(1C)亚单位(CaL-α_(1C))和Na^+-Ca^(2+)交换器(NCX)mRNA的变化影响,在基因水平探讨其潜在的意义。方法:Sprague-Dawley大鼠,高血压组用U型银夹夹住左肾动脉,右肾保留;假手术组(S组)只分离左肾动脉,不夹银夹,套尾法监测尾动脉血压。高血压组术后1周开始治疗,分为高剂量地尔硫(艹卓)组(HD组)、低剂量地尔硫(艹卓)组(LD组)和对照组(C组),分别于治疗后4周与S组同时处死动物(各6只),RT-PCR半定量分析CaL-α_(1C)和NCXmRNA的表达量(以GAPDH为内参照)。结果:C组心房肌CaL-α_(1C)的mRNA水平分别是S组、HD组、LD组的2.5倍、2.4倍、2.1倍(P<0.01),S组、HD组、LD组之间无显著差别。C组心房肌NCX的mRNA水平分别是S组、HD组、LD组的1.9倍、1.6倍、2.1倍(P<0.01),S组、HD组、LD组之间无显著差别。结论:肾性高血压大鼠心房肌CaL-α_(1C)、NCX的mRNA水平均表现为上调,应用钙拮抗剂能够抑制其上调,抑制作用不依赖于血压水平的降低。

AIM: To investigate the mRNA changes of L-type Ca^(2+) channel α_(1C) subunit (CaL-α_(1C)) and Na^+-Ca^(2+) exchanger (NCX) in the atria of renovascular hypertensive rats. METHODS: Two-kidney one-clip Goldblatt hypertensive Sprague-Dawley rats were divided into three groups 1 week after operation, HD group was treated with 250 mg/d diltiazem, LD group was treated with 50 mg/d diltiazem, control group (C group) was treated with vehicle. After 4 weeks treatment, semiquantitative RT-PCR was used to estimate the mRNA changes of CaL-α_(1C) and NCX, and GAPDH was used as internal control. RESULTS: Systolic blood pressure in LD group was comparable with C group, and that in HD group was decreased to normal level after diltiazem treatment. In C group, CaL-α_(1C) mRNA level were 2.5, 2.4 and 2.1 times of S, HD and LD group, and NCX mRNA level were 1.9, 1.6 and 2.1 times of S, HD and LD group. There were no significant difference in the mRNA level of CaL-α_(1C) and NCX among S, HD and LD group. CONCLUSION: The mRNA levels of CaL-α_(1C) and NCX are upregulated in the atria of hypertensive rats. Ca^(2+) antagonist inhibits their upregulation independent of blood pressure.