Kuo Fu-Chen, Wu Deng-Chyang, Yuan Shyng-Shiou F, Hsiao Kwo-Ming, Wang Yuan-Yung, Yang Yuan-Chieh, Lo Yi-Ching
Department of Gynecology and Obstetrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
J Perinat Med. 2005;33(5):399-405. doi: 10.1515/JPM.2005.072.
This study investigated the effects of arecoline, an active ingredient of the areca nut, on the tone of human umbilical arteries and veins and on the eNOS expression and cell proliferation of human umbilical vein endothelial cells (HUVECs). We found that arecoline relaxes the human umbilical artery and vein rings in a concentration-dependent manner; the higher the concentration of arecoline, the greater the relaxation of the rings. However, the relaxation decreases after the endothelium was removed or pretreated with L-NAME, a nitric oxide synthase inhibitor. Moreover, arecoline increases in a dose-dependent way the cGMP levels of human umbilical arteries and veins. In HUVECs, arecoline also increases the eNOS expression. Therefore, the relaxant effects of arecoline on the umbilical artery and vein rings were endothelium-dependent through the NO-cGMP systems. In addition, arecoline at higher doses (100-1000 microM) inhibits endothelial cell proliferation; the exposure toarecoline (100-1000 microM) for 24 and 48 h induces G2/M cell cycle arrest of HUVECs. Our results indicate that arecoline would decrease vascular tone, in part mediated by NO. Higher doses of arecoline inhibit endothelial cell growth, which suggest that long-term use or high doses of areca nut might induce endothelial dysfunction and associated diseases.
本研究调查了槟榔的活性成分槟榔碱对人脐动脉和静脉张力以及人脐静脉内皮细胞（HUVECs）中内皮型一氧化氮合酶（eNOS）表达和细胞增殖的影响。我们发现槟榔碱以浓度依赖的方式舒张人脐动脉和静脉环；槟榔碱浓度越高，环的舒张程度越大。然而，在内皮去除或用一氧化氮合酶抑制剂L-NAME预处理后，舒张作用减弱。此外，槟榔碱以剂量依赖的方式增加人脐动脉和静脉的环磷酸鸟苷（cGMP）水平。在HUVECs中，槟榔碱也增加eNOS表达。因此，槟榔碱对脐动脉和静脉环的舒张作用通过NO-cGMP系统依赖于内皮。此外，高剂量（100 - 1000微摩尔）的槟榔碱抑制内皮细胞增殖；暴露于槟榔碱（100 - 1000微摩尔）24小时和48小时会诱导HUVECs的G2/M期细胞周期阻滞。我们的结果表明，槟榔碱会降低血管张力，部分由NO介导。高剂量的槟榔碱抑制内皮细胞生长，这表明长期使用或高剂量的槟榔可能会诱导内皮功能障碍及相关疾病。
