Efficient inhibition of the development of cardiac remodeling by a long-acting calcium antagonist amlodipine.
Efficient inhibition of the development of cardiac remodeling by a long-acting calcium antagonist amlodipine.
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DOI：
10.1161/01.hyp.31.1.32
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发表时间：
1998
期刊：
影响因子：
8.3
通讯作者：
Tsutomu Yamazaki;Issei Komuro;Yunzeng Zou;S. Kudoh;I. Shiojima;T. Mizuno;Yukio Hiroi;R. Nagai;Yoshio Yazaki
中科院分区：
文献类型：
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作者：
Tsutomu Yamazaki;Issei Komuro;Yunzeng Zou;S. Kudoh;I. Shiojima;T. Mizuno;Yukio Hiroi;R. Nagai;Yoshio Yazaki
本研究的目的是观察长效钙拮抗剂氨氯地平对心脏重塑的影响。二氢吡啶类钙拮抗剂多年来被广泛应用于高血压和心绞痛的治疗。然而，据报道，二氢吡啶的原型硝苯地平并不能降低缺血性心脏病患者的死亡率，这可能是由于交感神经系统的反射刺激所致。据报道，一种名为氨氯地平的钙拮抗剂具有逐渐起效和持续时间长的潜在益处。12周龄自发性高血压大鼠给予氨氯地平(8 mg/kg/d，1次/d)或硝苯地平(24 mg/kg/d，3次/d)治疗12周。超声心动图测量左室壁厚度，焦磷酸盐凝胶测定肌球蛋白重链亚型的相对含量。Northern印迹法检测胎儿型基因和1型胶原基因的表达。氨氯地平和硝苯地平均显著降低收缩压。硝苯地平的降压作用持续时间不超过8h，而氨氯地平的降压作用持续时间超过16h。氨氯地平显著降低了左室壁厚度，而硝苯地平仅微弱地减弱了左室壁厚度的增加。氨氯地平但不能阻止V3肌球蛋白重链亚型相对量的增加，并抑制β-肌球蛋白重链、骨骼肌α-肌动蛋白和1型胶原基因水平的增加。与硝苯地平不同，氨氯地平在生化水平和形态水平上有效地预防了继发于高血压的心脏重构。这些结果表明，长效钙拮抗剂在预防高血压患者器官损伤方面比短效钙拮抗剂更有效。
The purpose of the present study was to examine the effects of a long-acting calcium antagonist, amlodipine, on the development of cardiac remodeling. Dihydropyridine calcium antagonists have been used widely for many years in the treatment of hypertension and angina pectoris. It has been reported, however, that a prototype of dihydropyridines, nifedipine, does not reduce mortality of patients with ischemic heart disease, possibly because of reflex stimulation of the sympathetic nervous system. A calcium antagonist, amlodipine, has been reported to have potential benefits by virtue of a gradual onset of action and a long duration of effects. Amlodipine (8 mg/kg per day, once a day) or nifedipine (24 mg/kg per day, three times a day) was administered to spontaneously hypertensive 12-week-old rats for 12 weeks. Left ventricular wall thickness was measured by echocardiography, and relative amounts of myosin heavy chain isoforms were assessed by pyrophosphate gels. Expressions of "fetal type" genes and type 1 collagen gene were examined by Northern blot analysis. Amlodipine and nifedipine both markedly reduced systolic blood pressure. However, the decrease in systolic blood pressure caused by nifedipine continued for no more than 8 hours, whereas the blood pressure-lowering effect of amlodipine continued for more than 16 hours post dose. Amlodipine markedly reduced left ventricular wall thickness, whereas nifedipine only weakly attenuated an increase in the wall thickness. Amlodipine, but not nifedipine, prevented an increase in the relative amount of V3 myosin heavy chain isoform and suppressed an increase in mRNA levels of beta-myosin heavy chain, skeletal alpha-actin, and type 1 collagen. Unlike nifedipine, amlodipine effectively prevented cardiac remodeling secondary to high blood pressure at biochemical levels and morphological levels. These results suggest that a long-acting calcium antagonist is more effective than a short-acting one in preventing organ injury in hypertensive subjects.