College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
J Ethnopharmacol. 2010 May 27;129(2):197-202. doi: 10.1016/j.jep.2010.03.003. Epub 2010 Mar 27.
The aim of the present study was to define the effects of extracts of leaves of Zanthoxylum piperitum (ZP) on the vascular tension and its mechanisms responsible in rat thoracic aortic rings.
Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) were examined for their vascular relaxant effects in isolated phenylephrine-precontracted aortic rings.
Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished the AZP-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N(G)-nitro-L-arginine methylester (L-NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the AZP-induced vasorelaxation. Inhibition of Ca(2+) entry via L-type Ca(2+) channels failed to block the AZP-induced vasorelaxation. Extracellular Ca(2+) depletion slightly but significantly attenuated the AZP-induced vasorelaxation. Thapsigargin significantly attenuated the AZP-induced vasorelaxation. Further, Gd(3+) and 2-aminoethyl diphenylborinate (2-APB), inhibitors of store-operated Ca(2+) entry (SOCE), markedly attenuated the AZP-induced vasorelaxation. Also, wortmannin, an inhibitor of Akt, an upstream signaling molecule of eNOS, attenuated the AZP-induced vasorelaxation. AZP increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by L-NAME, ODQ, thapsigargin, Gd(3+), 2-APB, and wortmannin. K(+) channel inhibition with glibenclamide and tetraethylammonium, cyclooxygenase inhibition with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the AZP-induced vasorelaxation.
Taken together, the present study suggests that AZP relaxes vascular smooth muscle via endothelium-dependent activation of NO-cGMP signaling through the Akt- and SOCE-eNOS pathways.
本研究旨在确定荜茇叶提取物（ZP）对大鼠胸主动脉环血管张力的影响及其作用机制。
检测 ZP 甲醇提取物和甲醇提取物的水相部分（AZP）对预先用苯肾上腺素收缩的主动脉环的血管舒张作用。
ZP 甲醇提取物和甲醇提取物的水相部分（AZP）以浓度依赖性方式诱导预先用苯肾上腺素收缩的主动脉环舒张。内皮细胞剥脱消除了 AZP 诱导的血管舒张。预先用 N(G)-硝基-L-精氨酸甲酯（L-NAME）和 1H-[1,2,4]-恶二唑-[4,3-α]-喹喔啉-1-酮（ODQ）处理完整内皮的主动脉环，抑制了 AZP 诱导的血管舒张。通过 L 型钙通道抑制钙内流未能阻断 AZP 诱导的血管舒张。细胞外钙耗竭轻微但显著减弱了 AZP 诱导的血管舒张。他帕昔琼显著减弱了 AZP 诱导的血管舒张。此外，钙库操纵性钙内流（SOCE）抑制剂 Gd(3+)和 2-氨基乙基二苯基硼酸盐（2-APB）明显减弱了 AZP 诱导的血管舒张。此外，Akt 的上游信号分子 eNOS 的抑制剂wortmannin 减弱了 AZP 诱导的血管舒张。AZP 以浓度依赖性方式增加主动脉环中环鸟苷酸（cGMP）的水平，该作用被 L-NAME、ODQ、他帕昔琼、Gd(3+)、2-APB 和 wortmannin 阻断。用格列本脲和四乙铵抑制钾通道、用吲哚美辛抑制环氧化酶以及阻断肾上腺素能和毒蕈碱受体对 AZP 诱导的血管舒张没有影响。
综上所述，本研究表明 AZP 通过 Akt 和 SOCE-eNOS 途径激活内皮依赖性一氧化氮-cGMP 信号转导来舒张血管平滑肌。
