Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release
Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release
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DOI：
10.1016/j.ejphar.2007.06.043
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发表时间：
2007-11-14
影响因子：
5
通讯作者：
Cao, Yong-Xiao
中科院分区：
文献类型：
--
作者：
He, Jian-Yu;Zhang, Wei;Cao, Yong-Xiao
本研究的目的是探讨欧前胡素对血管扩张的作用及其可能的机制。用肌图系统记录大鼠肠系膜动脉环的等长张力。结果表明，10 PM以上浓度依赖性欧前胡素可使大鼠肠系膜动脉（KCI）和内皮素-1预收缩，人大网膜动脉（去甲肾上腺素和U46619）预收缩。去除内皮不影响欧前胡素诱导的松弛反应，表明血管舒张作用与内皮无关。与欧前胡素共孵生导致KCI、氯化钙（CaCl2）和去甲肾上腺素的浓度-响应曲线非平行向右移动；10 μ M和30 μ M对5-羟色胺（5-HT）浓度-响应曲线平行右移，100 μ M对5-羟色胺（5-HT）浓度-响应曲线有明显抑制作用，说明欧前胡素的抑制作用主要是通过电压依赖性钙通道，也可能是通过受体操作的钙通道。p -肾上腺素能受体、atp敏感钾通道和内整流钾通道不参与血管舒张，而四乙基铵阻断钙活化钾通道有作用。此外，在无Ca2+的培养基中，欧前胡素浓度依赖性地抑制了由去甲肾上腺素和CaCl2引起的血管收缩，并导致咖啡因诱导的收缩反应减少，表明抑制细胞外Ca2+内流和细胞内Ca2+从Ca2+储存中释放的作用。综上所述，我们的研究结果表明，欧前胡素通过抑制电压依赖性钙通道和受体介导的Ca2+内流和Ca2+释放的可能机制诱导血管舒张。开放的钙活化钾通道和5-羟色胺受体的竞争性拮抗也可能有助于这种血管舒张作用。(c) 2007 Elsevier B.V.版权所有
The purpose of the present study was to investigate the effect of imperatorin on vasodilatation and its possible mechanisms. Isometric tension of rat mesenteric arterial rings was recorded by a myograph system in vitro. The results showed that imperatorin at more than 10 PM concentration-dependently relaxed rat mesenteric arteries pre-contracted by potassium chloride (KCI) and endothelin-1, and human omental arteries pre-contracted by noradrenaline and U46619. Removal of the endothelium did not affect imperatorin-induced relaxant responses, suggesting that the vasodilatation effect is independent of the endothelium. Co-incubation with imperatorin resulted in rightward shift of concentration-response curves of KCI, calcium chloride (CaCl2) and noradrenaline in a non-parallel manner; 5-hydroxytryptamine (5-HT) concentration-response curves were shifted towards right in a parallel manner by imperatorin 10 and 30 mu M, but markedly suppressed by imperatorin 100 mu M. These results suggest that the inhibitory effect of imperatorin is mainly via voltage dependent calcium channel and possibly receptor operated calcium channel. P-adrenoceptor, ATP-sensitive potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation, whereas blockage of calcium-activated potassium channel with tetraethylammonium had effect. Furthermore, in Ca2+-free medium, imperatorin concentration-dependently depressed the vasoconstrictions derived from noradrenaline and CaCl2 and resulted in a de creased contractile response induced by caffeine, indicating a role of inhibiting extracellular Ca2+ influx and intracellular Ca2+ release from Ca2+ store. Taken together, our results suggest that imperatorin induces vasodilatation by possible mechanisms inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and Ca2+ release. Opening calcium-activated potassium channel and competitive antagonism of 5-HT receptors may also contribute to this vasodilatation effect. (c) 2007 Elsevier B.V. All rights reserved.