Vascular endothelium and Ca2+ antagonists.
Vascular endothelium and Ca2+ antagonists.
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血管内皮和 Ca2 拮抗剂。
DOI：
10.1097/00005344-198812006-00007
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发表时间：
1988
影响因子：
3
通讯作者：
Vanhoutte,PM
中科院分区：
文献类型：
--
作者：
Vanhoutte,PM
内皮细胞可以释放舒张因子和收缩因子。由于内皮依赖性舒张因子的释放可通过在无Ca 2+溶液中孵育来阻止，并且可由Ca 2+离子载体A 23187触发，因此它必须需要内皮细胞中胞质Ca 2+浓度的增加。Ca 2+通道激动剂也会引起内皮依赖性舒张因子的释放，这种作用可被二氢吡啶类药物阻止;因此，内皮细胞膜必须含有电压操纵的Ca 2+通道。然而，由于维拉帕米和二氢吡啶不能阻止乙酰胆碱引起的内皮依赖性舒张因子的释放，因此导致介质释放的细胞质Ca 2+浓度增加不是由于这些通道的激活。地尔硫卓对内皮依赖性舒张因子的释放具有抑制作用，这不能归因于化合物对Ca 2+通道的作用。在存在功能性内皮的情况下，内皮依赖性舒张因子和Ca 2+拮抗剂如尼索地平在抑制血管平滑肌收缩方面是协同的。在各种动脉和静脉中，缺氧可诱发内皮依赖性收缩;这些收缩以及脑动脉牵拉诱发的内皮依赖性张力增加可被Ca 2+拮抗剂抑制。在自发性高血压大鼠的主动脉中，乙酰胆碱引起内皮依赖性收缩，这种作用被地尔硫卓抑制。从缺氧冠状动脉实验判断，Ca 2+拮抗剂对内皮依赖性收缩的抑制作用是在血管平滑肌水平，而不是内皮。因此。Ca 2+拮抗剂不阻止内皮依赖性舒张因子或内皮依赖性收缩因子的释放;通过促进前者的抑制作用，并阻止后者激活血管平滑肌，它们有利于扩张的发生。
Endothelial cells can release both relaxing and contracting factors. Since the release of endothelium-dependent relaxing factor is prevented by incubation in Ca 2†-free solution and can be triggered by the Ca 2† ionophore A 23187, it must require an increase in cytoplasmic Ca 2† concentration in the endothelial cells. Ca 2†-channel agonists also evoke the release of endothelium-dependent relaxing factor, an effect prevented by dihydropyridines; thus, the endothelial cell membrane must contain voltage-operated Ca 2† channels. However, since verapamil and dihydropyridines do not prevent the release of endothelium-dependent relaxing factor evoked by acetylcholine, the increase in cytoplasmic Ca 2† concentration leading to the release of the mediator is not due to activation of these channels. Diltiazem has an inhibitory effect on the release of endothelium-dependent relaxing factor, which cannot be attributed to the action of the compound at Ca 2† channels. In the presence of functional endothelium, endothelium-dependent relaxing factor and Ca 2† antagonists such as nisoldipine are synergistic in inhibiting contractions of vascular smooth muscle. In a variety of arteries and veins, endothelium-dependent contractions can be evoked by anoxia; these contractions, as well as the endothelium-dependent increases in tension evoked by stretch in cerebral arteries, can be inhibited by Ca 2† antagonists. In the aorta of the spontaneously hypertensive rat, acetylcholine causes endothelium-dependent contractions, an effect that is inhibited by diltiazem. To judge from experiments in anoxic coronary arteries, the inhibitory effect of Ca 2† antagonists on endothelium-dependent contractions is at the level of the vascular smooth muscle, and not the endothelium. Thus. Ca 2† antagonists do not prevent the release of either endothelium-dependent relaxing factor or endothelium-dependent contracting factor; by facilitating the inhibition exerted by the former, and preventing the activation of vascular smooth muscle by the latter, they favor the occurrence of dilatation.