Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Phytother Res. 2018 Feb;32(2):267-275. doi: 10.1002/ptr.5969. Epub 2017 Nov 29.
In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K channels, BK channels, and at least partly, K channels. In addition, not only the inhibition of extracellular Ca influx, but regulation of the intracellular Ca release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.
在这项研究中，我们旨在研究黄烷醇 (-)-表儿茶素对分离的人隐静脉 (HSV) 的松弛作用，作为其心脏保护作用的一部分，并确定这种血管松弛的机制。(-)-表儿茶素诱导 HSV 对苯肾上腺素预收缩的浓度依赖性松弛。在 K 通道阻滞剂中，4-氨基吡啶、马加毒素和iberiotoxin 显著抑制 HSV 的松弛，而格列本脲则大大降低了 (-)-表儿茶素高浓度的作用。此外，(-)-表儿茶素松弛由 80 mM K 诱导的收缩，而在硝苯地平存在下，部分松弛苯肾上腺素预收缩的 HSV 环。在无钙溶液中，(-)-表儿茶素松弛苯肾上腺素诱导的收缩，但对咖啡因诱导的收缩没有影响。肌浆网 Ca-ATP 酶抑制剂 thapsigargin 显著降低 (-)-表儿茶素产生的 HSV 松弛。这些结果表明，(-)-表儿茶素产生内皮细胞独立的分离 HSV 环松弛。(-)-表儿茶素引起的血管松弛可能涉及激活 4-氨基吡啶和马加毒素敏感的 K 通道、BK 通道，至少部分涉及 K 通道。此外，不仅通过抑制细胞外 Ca 内流，而且通过肌浆网内 Ca 释放的调节，通过三磷酸肌醇受体和通过 Ca-ATP 酶的刺激，再摄取到肌浆网中，也可能参与 (-)-表儿茶素诱导的 HSV 松弛。
