Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids.
Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids.
复制标题
硝苯地平可改善高胆固醇血症的内皮功能，与血压或血脂的影响无关。
DOI：
10.1016/s0008-6363(98)00341-1
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发表时间：
1999
影响因子：
10.8
通讯作者：
T. Rabelink
中科院分区：
文献类型：
--
作者：
M. Verhaar;M. Honing;T. Dam;M. Zwart;Hendrik A. Koomans;J. Kastelein;T. Rabelink
目的：二氢吡啶类钙拮抗剂可以延缓动物模型的动脉粥样硬化形成，防止人类冠状动脉早期病变的发生。内皮功能障碍是心血管疾病发病机制中的早期事件。方法：首先，我们比较了11例家族性高胆固醇血症患者服用硝苯地平控释片(60 mg，OD)治疗6周前后和12名对照组前臂血管对内皮依赖性和非依赖性血管扩张剂5-羟色胺(5-HT)和硝普钠(SNP)的反应。在6名对照组受试者中，前臂血管功能也在硝苯地平控释片治疗前和治疗6周后进行了评估。在体外，我们随后探索了硝苯地平对内皮功能影响的可能机制。结果：高胆固醇血症患者前臂血流增加47±9%，对照组前臂血流增加99±8%。硝苯地平可完全恢复5-羟色胺引起的血管扩张(113±13%)，但不影响前臂基础血管运动和硝普钠引起的血管扩张。硝苯地平不改变对照组受试者的前臂血管反应，也不改变血压或血脂。在体外，我们没有发现硝苯地平对重组eNOS或血管内皮细胞产生NO的直接影响。然而，我们确实观察到内皮细胞超氧化物的生成减少。结论：我们的数据显示，硝苯地平改善了高胆固醇血症患者的内皮功能。我们的体外实验表明，这种作用是由于减少了NO的降解。
Objective:Dihydropyridine calcium antagonists have been shown to retard atherogenesis in animal models and to prevent the development of early angiographic lesions in human coronary arteries. Endothelial dysfunction is an early event in the pathogenesis of cardiovascular disease. We investigated whether nifedipine could improve endothelial function in hypercholesterolemia, independently of changes in blood pressure or plasma lipids.Methods:First, we compared in vivo forearm vascular responses to the endothelium-dependent and independent vasodilators serotonin (5-HT) and sodium nitroprusside (SNP) in 11 patients with familial hypercholesterolemia before and after 6-weeks treatment with nifedipine GITS (60 mg, OD) and in 12 matched controls. In a subgroup of six control subjects forearm vascular function was also assessed before and after 6-weeks nifedipine GITS treatment. In vitro, we subsequently explored possible mechanisms underlying the effect of nifedipine on endothelial function. We investigated the effects of nifedipine on both NO production by recombinant endothelial NO synthase (eNOS) and endothelial cells, using3H-arginine conversion, as well as on superoxide generation by endothelial cell lysates, using lucigenin enhanced chemiluminescence.Results:In hypercholesterolemia 5-HT-induced vasodilation was impaired (47±9% increase in forearm bloodflow vs. 99±8% in controls). Treatment with nifedipine completely restored 5-HT-induced vasodilation (113±13%), whereas it did not influence basal forearm vasomotion or SNP-induced vasodilation. Nifedipine did not alter forearm vascular responses in control subjects and did not alter blood pressure or plasma lipids. In vitro, we found no direct effect of nifedipine on NO production by recombinant eNOS or endothelial cells. However, we did observe a reduction in endothelial superoxide generation.Conclusions:Our data show that nifedipine improves endothelial function in hypercholesterolemia. It is suggested from our in vitro experiments that this effect is due to reduced NO degradation.
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影响因子：
37.8
作者：
Xiaoping Zhang;T. Hintze
通讯作者：
Xiaoping Zhang;T. Hintze
影响因子：
37.8
作者：
H. Ting;Farris K Timimi;Elizabeth A. Haley;M. Roddy;P. Ganz;M. Creager
通讯作者：
H. Ting;Farris K Timimi;Elizabeth A. Haley;M. Roddy;P. Ganz;M. Creager
影响因子：
2.8
作者：
HARRISON, DG;OHARA, Y
通讯作者：
OHARA, Y
影响因子：
158.5
作者：
ANDERSON, TJ;MEREDITH, IT;GANZ, P
通讯作者：
GANZ, P
影响因子：
37.8
作者：
Davis, SF;Yeung, AC;Anderson, TJ
通讯作者：
Anderson, TJ