Yamada Y, Yokota M, Furumichi T, Furui H, Yamauchi K, Saito H
Nagoya University School of Medicine, Japan.
Cardiovasc Res. 1990 Dec;24(12):993-7. doi: 10.1093/cvr/24.12.993.
The aim was to examine the effects of calcium channel blockers on the permeability of endothelial cells and to determine whether these agents could protect against increases in endothelial permeability induced by hydrogen peroxide (H2O2).
Endothelial cells were cultured on collagen coated micropore filters. When they were confluent on the filter, albumin transfer and electrical resistance across the endothelial monolayers were measured.
Endothelial cells were obtained from human umbilical veins. The cells at the 2nd to 4th passage were used for the experiments.
Nilvadipine (10(-8) M) suppressed endothelial albumin transfer by 37.2% (p less than 0.01) and enhanced electrical resistance by 25.8% (p less than 0.01), whereas nicardipine (10(-7) M), diltiazem (10(-7) M), and verapamil (10(-7) M) had no significant effect on either variable without the addition of H2O2. H2O2(0.2 mM) increased albumin transfer by 164% (p less than 0.01) and reduced electrical resistance by 67% (p less than 0.01) across endothelial monolayers without endothelial cell lysis. Nilvadipine (10(-8) M) and nicardipine (10(-7) M) inhibited the (0.2 mM) H2O2 induced increases in endothelial albumin transfer and decreases in electrical resistance more strongly than diltiazem and verapamil, although all of these agents significantly reduced such injury.
Nilvadipine is a potent inhibitor of endothelial permeability and of hydrogen peroxide induced increases in permeability.
本研究旨在探讨钙通道阻滞剂对内皮细胞通透性的影响，并确定这些药物是否能预防过氧化氢（H2O2）诱导的内皮通透性增加。
将内皮细胞培养在胶原包被的微孔滤膜上。当细胞在滤膜上汇合后，测量白蛋白转运以及跨内皮单层的电阻。
内皮细胞取自人脐静脉。使用第2至4代细胞进行实验。
尼伐地平（10(-8) M）可使内皮白蛋白转运抑制37.2%（p<0.01），电阻增加25.8%（p<0.01）；而尼卡地平（10(-7) M）、地尔硫䓬（10(-7) M）和维拉帕米（10(-7) M）在未添加H2O2时对上述两个指标均无显著影响。H2O2（0.2 mM）可使内皮单层白蛋白转运增加164%（p<0.01），电阻降低67%（p<0.01），且未引起内皮细胞裂解。尼伐地平（10(-8) M）和尼卡地平（10(-7) M）比地尔硫䓬和维拉帕米更能有效抑制（0.2 mM）H2O2诱导的内皮白蛋白转运增加和电阻降低，尽管所有这些药物均能显著减轻这种损伤。
尼伐地平是内皮通透性及过氧化氢诱导的通透性增加的有效抑制剂。
