Luteolin-induced coronary arterial relaxation involves activation of the myocyte voltage-gated K+ channels and inward rectifier K+ channels
Luteolin-induced coronary arterial relaxation involves activation of the myocyte voltage-gated K+ channels and inward rectifier K+ channels
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木犀草素诱导的冠状动脉舒张涉及肌细胞电压门控 K 通道和内向整流 K 通道的激活
DOI：
10.1016/j.lfs.2019.02.028
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发表时间：
2019-03-15
期刊：
影响因子：
6.1
通讯作者：
Zhang, Mingsheng
中科院分区：
文献类型：
--
作者：
Li, Weiping;Dong, Miaomiao;Zhang, Mingsheng
目的：木犀草素对心血管组织和器官有保护作用。本研究旨在观察其对不同缩血管剂的血管痉挛作用及其对新鲜分离的大鼠冠状动脉平滑肌细胞（RCASMCs）电压门控钾（Kv）通道和内向整流钾（Kir）通道钾电流的影响。结果：毛地黄黄酮预孵育可抑制KCl、血栓素A（2）类似物U46619、加压素、Kir阻断剂BaCl 2、Kv阻断剂4-氨基吡啶引起的RCASMCs收缩，并抑制高钾去极化液中细胞外钙离子（[Ca 2 +]（o））的升高。即时应用木犀草素产生浓度依赖性舒张的内皮剥脱RCA预收缩与KCl或U46619。4-氨基吡啶和氯化钡均能减弱木犀草素诱导的U46619预收缩RCA的舒张作用，而一氧化氮合成酶抑制剂NG-硝基-L-精氨酸甲酯和环氧合酶抑制剂吲哚美辛均不影响这种舒张作用。木犀草素能增强RCASMCs的Kv和Kir电流，其增强作用分别被4-氨基吡啶和BaCl_2所拮抗。意义：本实验结果表明木犀草素能拮抗RCAs的多种缩血管物质，并能增强RCASMCs的Kv和Kir电流，提示木犀草素对Kv和Kir通道的直接作用是其血管痉挛作用的一部分。这些结果表明，毛地黄黄酮可能是一个有前途的食品添加剂，目的是预防冠状动脉痉挛。
Aims: Luteolin has been shown to be beneficial to cardiovascular tissues and organs. We aimed to study its vasospasmolytic effects against various vasoconstrictors in the isolated rat coronary arteries (RCAs) and its electrophysiological effects on K+ currents via voltage-gated potassium (Kv) channels and inward rectifier potassium (Kir) channels in freshly isolated rat coronary arterial smooth muscle cells (RCASMCs).Main methods: The vascular tone of the endothelium-denuded RCAs was recorded by a wire myograph. Kv currents and Kir currents in RCASMCs were assessed using whole-cell patch clamp.Key findings: Preincubation with luteolin depressed the contractions elicited by KCl, thromboxane A(2) analog U46619, vasopressin, Kir blocker BaCl2, Kv blocker 4-aminopyridine and elevation of extracellular calcium ([Ca2+](o)) in high K+ depolarizing solution. Instant application of luteolin produced concentration-dependent relaxations in the endothelium-denuded RCAs precontracted with KCl or U46619. Both 4-aminopyridine and BaCl2 attenuated luteolin-induced relaxation in U46619-precontracted RCAs, while neither nitric oxide synthetase inhibitor NG-nitro-L-arginine methyl ester nor cyclooxygenase inhibitor indomethacin affected the relaxation. Luteolin augmented both Kv currents and Kir currents in RCASMCs and the augmentations were antagonized by 4-aminopyridine and BaCl2, respectively.Significance: The present results demonstrated that luteolin antagonizes various vasoconstrictors in RCAs and augments both Kv currents and Kir currents in RCASMCs, suggesting that the direct action of luteolin on Kv channels and Kir channels is contributory to its vasospasmolytic effect. These findings indicate that luteolin may be a promising food additive with the aim of preventing coronary arterial spasm.