Waters D, Lespérance J
Division of Cardiology, Hartford Hospital, CT 06102-5037.
Am Heart J. 1994 Dec;128(6 Pt 2):1309-16. doi: 10.1016/0002-8703(94)90253-4.
Many calcium channel blockers have been shown to retard the development of atherosclerosis in cholesterol-fed rabbits. The mechanisms that may contribute to this effect include stimulation of cholesteryl ester hydrolase activity in smooth muscle cells, amelioration of hypercholesterolemic-induced endothelial dysfunction, or inhibition of smooth muscle cell proliferation and migration. The effect of calcium channel blockers on the evolution of coronary atherosclerosis in humans has been assessed in three clinical trials. In the Montreal Heart Institute trial, nicardipine did not influence the overall rate of progression and regression; however, patients treated with nicardipine experienced significantly less progression of minimal lesions, defined as stenoses of less than or equal to 20% severity. In the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT), nifedipine had no effect on overall progression and regression but, by one method of analysis, reduced the rate of appearance of new coronary lesions. In a preliminary report, diltiazem prevented the development of coronary atherosclerosis in heart transplant recipients. These studies indicate that calcium channel blockers retard the development of early atherosclerosis not only in animal models but also in human coronary arteries. Other studies recently completed or now under way will help to clarify the clinical role of calcium channel blockers in antiatherosclerotic therapy.
许多钙通道阻滞剂已被证明可延缓胆固醇喂养的兔子动脉粥样硬化的发展。可能导致这种作用的机制包括刺激平滑肌细胞中的胆固醇酯水解酶活性、改善高胆固醇血症诱导的内皮功能障碍，或抑制平滑肌细胞增殖和迁移。三项临床试验评估了钙通道阻滞剂对人类冠状动脉粥样硬化进展的影响。在蒙特利尔心脏研究所的试验中，尼卡地平不影响总体进展和消退率；然而，接受尼卡地平治疗的患者病变程度小于或等于20%的轻微病变进展明显较少。在国际硝苯地平抗动脉粥样硬化治疗试验（INTACT）中，硝苯地平对总体进展和消退没有影响，但通过一种分析方法，降低了新冠状动脉病变的出现率。在一份初步报告中，地尔硫卓可预防心脏移植受者冠状动脉粥样硬化的发展。这些研究表明，钙通道阻滞剂不仅在动物模型中，而且在人类冠状动脉中均可延缓早期动脉粥样硬化的发展。最近完成或正在进行的其他研究将有助于阐明钙通道阻滞剂在抗动脉粥样硬化治疗中的临床作用。
