Mutoh S, Nomoto A, Sekiguchi C, Yamaguchi I
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Atherosclerosis. 1988 Oct;73(2-3):181-9. doi: 10.1016/0021-9150(88)90040-8.
Nilvadipine and other calcium antagonists were studied for their effect on 1-alpha-hydroxyvitamin D3 (1 - alpha (OH)D3)-induced aortic calcium deposition in rats. The animals were treated orally with 1-alpha (OH)D3 (10 micrograms/kg) for 2 weeks. Calcium antagonists were given orally twice a day during the same period. The aortic calcium content in 1-alpha (OH)D3-treated rats increased to about 100 times that in the control. Nilvadipine reduced the aortic calcium deposition dose-dependently, with percent inhibition of 6, 43, 72 and 92%, at doses of 0.1, 1, 10 and 100 mg/kg, respectively. Similar activities were obtained for the other calcium antagonists except diltiazem which had no effect even at the largest dose of 100 mg/kg. According to the ED50 values, nilvadipine (2.2 mg/kg) was more potent than nifedipine (23.2 mg/kg), nicardipine (12.4 mg/kg) and verapamil (32.0 mg/kg). Scanning and transmission electron microscopy showed clear-cut degenerative changes in the endothelial cells after 1-alpha (OH)D3 treatment. Nilvadipine exerted a protective effect against these degenerative changes but not against 1-alpha (OH)D3-induced hypercalcemia. Furthermore, the drug had only minimal effect on in vitro calcification of the aorta. Our findings suggest that nilvadipine inhibits aortic calcification by protecting the aortic wall cells.
研究了尼伐地平及其他钙拮抗剂对1α-羟基维生素D3（1α(OH)D3）诱导的大鼠主动脉钙沉积的影响。给动物口服1α(OH)D3（10微克/千克），持续2周。在此期间，钙拮抗剂每天口服两次。1α(OH)D3处理的大鼠主动脉钙含量增加至对照大鼠的约100倍。尼伐地平剂量依赖性地降低主动脉钙沉积，在剂量分别为0.1、1、10和100毫克/千克时，抑制率分别为6%、43%、72%和92%。除地尔硫䓬外，其他钙拮抗剂也有类似作用，地尔硫䓬即使在最大剂量100毫克/千克时也无作用。根据半数有效剂量（ED50）值，尼伐地平（2.2毫克/千克）比硝苯地平（23.2毫克/千克）、尼卡地平（12.4毫克/千克）和维拉帕米（32.0毫克/千克）更有效。扫描和透射电子显微镜显示，1α(OH)D3处理后内皮细胞出现明显的退行性变化。尼伐地平对这些退行性变化有保护作用，但对1α(OH)D3诱导的高钙血症无保护作用。此外，该药物对主动脉的体外钙化作用极小。我们的研究结果表明，尼伐地平通过保护主动脉壁细胞来抑制主动脉钙化。
