Watanabe N, Ishikawa Y, Okamoto R, Watanabe Y, Fukuzaki H
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Artery. 1987;14(5):283-94.
We studied the effects of nifedipine, a calcium antagonist, on atherosclerosis in cholesterol-fed rabbits and Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Japanese White rabbits were fed 120g of 2% cholesterol rabbit chow daily, and WHHL rabbits were fed standard rabbit chow. In each experiment, the rabbits were divided into two groups. Twenty milligrams of nifedipine was given orally twice a day to the nifedipine group, and the control group was given a placebo in the same way. The rabbits were sacrificed at the end of the 12th week in the case of cholesterol-fed rabbits, and the 20th week in the case of WHHL rabbits. Among the cholesterol-fed rabbits, the percentage of aortic intimal surface area covered by atherosclerotic lesions (AS%) was 25.9 +/- 7.6% (mean +/- S.D.) in the nifedipine group (n = 7), and 55.6 +/- 22.8% in the placebo group (n = 8) (p less than 0.01). The cholesterol content of thoracic and abdominal aorta in the nifedipine group was lower than those in the placebo group (p less than 0.05). Among the WHHL rabbits, the AS% was 33.4 +/- 14.1% in the nifedipine group (n = 5), and 27.0 +/- 11.7% in the placebo group (n =6) (n.s.). The aortic cholesterol and calcium contents also showed no significant differences between the two groups. We concluded that nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in WHHL rabbits. The different responses suggest that the effect of nifedipine could be mediated by low density lipoprotein receptors or that the early exposure to hyperlipidemic serum from birth might affect cell functions of WHHL rabbits.
我们研究了钙拮抗剂硝苯地平对喂饲胆固醇的家兔和渡边遗传性高脂血症家兔（WHHL家兔）动脉粥样硬化的影响。给日本白兔每日喂饲120克含2%胆固醇的兔饲料，给WHHL家兔喂饲标准兔饲料。在每个实验中，将家兔分为两组。硝苯地平组家兔每天口服20毫克硝苯地平，每日两次，对照组以同样方式给予安慰剂。喂饲胆固醇的家兔在第12周结束时处死，WHHL家兔在第20周结束时处死。在喂饲胆固醇的家兔中，硝苯地平组（n = 7）动脉粥样硬化病变覆盖的主动脉内膜表面积百分比（AS%）为25.9 +/- 7.6%（平均值 +/- 标准差），安慰剂组（n = 8）为55.6 +/- 22.8%（p < 0.01）。硝苯地平组胸主动脉和腹主动脉的胆固醇含量低于安慰剂组（p < 0.05）。在WHHL家兔中，硝苯地平组（n = 5）的AS%为33.4 +/- 14.1%，安慰剂组（n = 6）为27.0 +/- 11.7%（无显著性差异）。两组间主动脉胆固醇和钙含量也无显著差异。我们得出结论，硝苯地平可抑制喂饲胆固醇家兔的动脉粥样硬化，但对WHHL家兔无效。不同的反应表明，硝苯地平的作用可能由低密度脂蛋白受体介导，或者出生后早期暴露于高脂血症血清可能影响WHHL家兔的细胞功能。
