Role of calcium in endothelium-dependent relaxation of arterial smooth muscle.
Role of calcium in endothelium-dependent relaxation of arterial smooth muscle.
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钙在动脉平滑肌内皮依赖性松弛中的作用。
DOI：
10.1016/0002-9149(87)90174-3
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Loeb,AL
中科院分区：
文献类型：
--
作者：
Peach,MJ;Singer,HA;IzzoJr,NJ;Loeb,AL
研究了兔胸主动脉环内皮依赖性松弛。甲胆碱、钙离子载体A23187和maitotoxin分别在Ca++去除前后诱导松弛反应；存在钙通道进入阻滞剂（维拉帕米和硝苯地平）；或者用三氟拉嗪。Ca++的缺失大大削弱了对所有3种激动剂的反应，而三氟拉嗪仅阻断胆碱能诱导的松弛。钙通道阻滞剂具有浓度和时间依赖性，但其作用包括阻断A23187。用10 μM Fura-2/AM或50 μM Quin -2/AM培养内皮细胞后，测定细胞内游离钙浓度。缓激素（1 × 10−10 ~ 1 × 10−7M）和蜂毒素（0.5 ~ 5 μg/ml）引起细胞内钙离子浓度呈剂量依赖性升高，分别在3 × 10−8M和3 μg/ml时达到最大。在EGTA （1.5 × 10−3M）或维拉帕米（1 × 10−5M）存在的情况下，这两种药物都能诱导细胞质游离Ca++的增加。维拉帕米对Ca++瞬态的平台期有轻微的改变，而Ca++/EGTA对峰值响应和平台期有减弱作用。为了评估内皮的功能，研究了在柱上监督的微载体珠上生长的细胞中内皮来源的松弛因子（EDRF）的产生，并在主动脉环上对柱流出物进行了生物测定。用于研究受体介导的细胞内钙离子变化的细胞在缓激肽和A23187的作用下产生并释放EDRF。EDRF的释放需要细胞外ca2 +。无细胞质钙离子的增加与牛和兔主动脉内皮产生或释放EDRF有关。
Endothelium-dependent relaxation was studied in rings of rabbit thoracic aorta. Relaxation responses were induced with methacholine, the calcium ionophore A23187 and maitotoxin before and after removal of Ca++from the external medium; in the presence of calcium-channel entry blockers (verapamil and nifedipine); or with trifluoperazine. Deletion of Ca++greatly impaired responses to all 3 agonists while trifluoperazine only blocked cholinergic-induced relaxation. The calcium-channel blockers had effects that were concentration- and time-dependent, but their action included blockade of A23187. Cytosolic-free Ca++concentrations were measured in cultured endothelial cells after incubation of the cells with 10 μM Fura-2/AM or 50 μM Quin 2/AM. Bradykinin (1 × 10−10to 1 × 10−7M) and melittin (0.5 to 5 μg/ml) caused dose-dependent increases in intracellular Ca++with maximal responses at 3 × 10−8M and 3 μg/ml, respectively. Both agents were able to induce an increase in cytosolic-free Ca++in the presence of EGTA (1.5 × 10−3M) or verapamil (1 × 10−5M). The plateau phase of the Ca++transient appeared to be modified slightly by verapamil, while the peak responses and plateau were attenuated by ‘0’ Ca++/EGTA. To assess a function of the endothelium, production of endothelium-derived relaxing factor (EDRF) was studied in cells grown on microcarrier beads supervised in a column, and the column effluent was bioassayed on aortic rings. The cells used in studies of receptor-mediated changes in intracellular Ca++produced and released EDRF in response to bradykinin and A23187. The EDRF release required extracellular Ca++. An increase in cytosolic-free Ca++correlated with the production or release of EDRF by bovine and rabbit aortic endothelium.