Effects of trans- and cis-resveratrol on Ca2+ handling in A7r5 vascular myocytes
Effects of trans- and cis-resveratrol on Ca2+ handling in A7r5 vascular myocytes
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DOI：
10.1016/j.ejphar.2007.08.003
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发表时间：
2007-12-22
影响因子：
5
通讯作者：
Orallo, Francisco
中科院分区：
文献类型：
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作者：
Campos-Toimil, Manuel;Elies, Jacobo;Orallo, Francisco
尽管天然多酚白藜芦醇具有直接的血管松弛作用，但其对血管细胞内钙离子浓度([Ca(2+)](I))的影响仍不清楚。在这里，我们用成像和膜片钳技术研究了反式和顺式白藜芦醇对激动剂和高K+诱导的血管A7r5细胞[Ca~(2+)]升高和电压激活的跨膜Ca~(2+)通量的影响。精氨酸加压素(AVP)或血管紧张素II引起细胞内钙离子双相升高，这种升高可被反式白藜芦醇和顺式白藜芦醇预先孵育所降低。两种异构体均可降低无细胞外钙时激动剂引起的[Ca~(2+)](I)升高。在高K+无Ca~(2+)溶液中，重新引入Ca~(2+)可引起[Ca~(2+)]~(2+)持续升高，而反式白藜芦醇或顺式白藜芦醇可使[Ca~(2+)]~(2+)持续升高。当在激动剂的平台期或高K+诱导的反应中应用异构体时，观察到[Ca~(2+)](I)的两相变化：平台期短暂降低(~lt；5min)，然后升高(~gt；10min)。最后，反式白藜芦醇和顺式白藜芦醇抑制电压依赖性L钙电流(L)。综上所述，白藜芦醇异构体对A7r5心肌细胞[Ca~(2+)](I)的处理具有双重作用：1)阻断[Ca~(2+)](L)；(2)通过耗尽细胞内钙库(干扰激动剂诱导的细胞内Ca~(2+)释放)和钙内流而增加[Ca~(2+)](I)，这主要是由于激活了容积性Ca~(2+)内流，尽管也涉及其他钙离子通透通道。综上所述，这些作用可能部分解释了白藜芦醇在大鼠主动脉中的非内皮依赖性血管松弛作用。(C)2007 Elsevier B.V.保留所有权利。
Although the natural polyphenol resveratrol posses a direct vasorelaxant effect, its effects on cytoplasmic Ca2+ concentration ([Ca (2+)](i)) in vascular cells remain still unclear. Here, we have investigated the effects of the isomers trans- and cis-resveratrol on agonist- and high-K+-induced [Ca2+], increases and on voltage-activated transmembrane Ca2+ fluxes using imaging and patch-clamp techniques in vascular A7r5 myocytes. Arginine vasopressin (AVP) or angiotensin II caused a biphasic increase in [Ca2+](i) that was reduced by preincubation with trans-resveratrol and cis-resveratrol. Both isomers also reduced the agonist-induced increase in [Ca2+](i) in absence of extracellular Ca2+. In high-K+ Ca2+-free solution, reintroduction of Ca2+ caused a sustained rise in [Ca2+](i) that was reduced by preincubation with trans-resveratrol or cis-resveratrol. When the isomers were applied during the plateau phase of the agonist- or the high-K+-induced response, a biphasic change in [Ca2+](i) was observed: a transient reduction of the plateau (< 5 min) followed by an increase (> 10 min). Finally, trans-resveratrol and cis-resveratrol inhibited voltage-dependent L-type Ca2+ currents (I-Ca(L)). In conclusion, resveratrol isomers exert a dual effect on [Ca2+](i) handling in A7r5 myocytes: 1) a blockade of I-Ca(L) and 2) an increase in [Ca2+](i) by depletion of intracellular Ca2+ stores (which interferes with the agonist-induced release of intracellular Ca2+) and influx of Ca, mainly due to activation of capacitative Ca2+ entry, although other Ca2+-permeable channels are also involved. Taken together, these effects may explain, in part, the endothelium-independent vasorelaxant effects of resveratrol in rat aorta. (c) 2007 Elsevier B.V. All rights reserved.