Ouchi Y, Orimo H
Department of Geriatric Medicine, Faculty of Medicine, University of Tokyo, Japan.
J Cardiovasc Pharmacol. 1990;16 Suppl 2:S1-4.
Results of animal studies suggest that calcium antagonists can inhibit the development of experimentally induced atherosclerosis. Although the biological process underlying this phenomenon has not been fully elucidated, several mechanisms have been proposed. Notably, calcium antagonists may suppress free radical-induced damage of the vascular endothelial cells with the consequent transport of low-density lipoproteins across the vascular endothelium and the accumulation of the lipids in the intima. Studies have shown that calcium antagonists can inhibit the stimulatory effects of epidermal growth factor on intracellular calcium concentrations and DNA synthesis in cultured rat aortic smooth muscle cells, but not those of platelet-derived growth factor or somatomedin C. Further experimental studies have demonstrated that calcium antagonists stimulate prostacyclin production and inhibit 12-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration, therefore preventing platelet aggregation and intimal thickening, respectively. Despite the encouraging results in animals, comparatively few clinical studies have been undertaken to establish the efficacy of calcium antagonists in the prevention of cardiovascular disease in hypertensive patients. This, in part, is due to the technical difficulties associated with measuring coronary artery stenosis, but the recent development of a technique for the video-densitometric analysis of coronary angiograms has enabled stenotic regions to be quantified. Using this approach, a retrospective study has been undertaken of the efficacy of long-term treatment with a calcium antagonist on the progression of coronary atherosclerosis. Results are encouraging and a prospective long-term, multicenter trial is proposed.
动物研究结果表明，钙拮抗剂可以抑制实验性动脉粥样硬化的发展。虽然这一现象背后的生物学过程尚未完全阐明，但已提出了几种机制。值得注意的是，钙拮抗剂可能抑制自由基诱导的血管内皮细胞损伤，从而导致低密度脂蛋白穿过血管内皮运输以及脂质在内膜中蓄积。研究表明，钙拮抗剂可以抑制表皮生长因子对培养的大鼠主动脉平滑肌细胞内钙浓度和DNA合成的刺激作用，但对血小板衍生生长因子或生长调节素C无此作用。进一步的实验研究表明，钙拮抗剂可刺激前列环素生成并抑制12-羟基二十碳四烯酸诱导的血管平滑肌细胞迁移，从而分别防止血小板聚集和内膜增厚。尽管在动物实验中取得了令人鼓舞的结果，但相对较少有临床研究来确定钙拮抗剂在预防高血压患者心血管疾病方面的疗效。部分原因是与测量冠状动脉狭窄相关的技术困难，但最近冠状动脉造影视频密度分析技术的发展使得能够对狭窄区域进行量化。采用这种方法，已经对钙拮抗剂长期治疗对冠状动脉粥样硬化进展的疗效进行了一项回顾性研究。结果令人鼓舞，因此提出了一项前瞻性长期多中心试验。
