Kang Le Xin Reduces Blood Pressure Through Inducing Endothelial-Dependent Vasodilation by Activating the AMPK-eNOS Pathway
Kang Le Xin Reduces Blood Pressure Through Inducing Endothelial-Dependent Vasodilation by Activating the AMPK-eNOS Pathway
复制标题
康乐欣通过激活 AMPK-eNOS 通路诱导内皮依赖性血管舒张来降低血压
DOI：
10.3389/fphar.2019.01548
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Baofeng Yang
中科院分区：
文献类型：
--
作者：
Yixiu Zhao;Jiuxin Zhu;Hangfei Liang;Shuang Yang;Yanna Zhang;Weina Han;Chao Chen;Na Cao;Aruhan;Peiqiang Liang;Xing Du;Jian Huang;Jinhui Wang;Yan Zhang;Baofeng Yang
高血压是临床上脑卒中和心血管事件的主要危险因素，并伴有血管张力异常和小动脉内皮功能障碍。本文报道了一种新型蒽醌类化合物康乐新（KLX）的降血压作用，其机制与诱导内皮依赖性血管舒张有关。KLX能显著降低自发性高血压大鼠（SHR）的动脉血压，降低肠系膜上级动脉对苯肾上腺素的收缩反应性，增加肠系膜上级动脉对卡巴胆碱的舒张反应性，并呈剂量依赖性。KLX能剂量依赖性地降低苯肾上腺素预收缩的内皮完整肠系膜动脉的血管张力，而这种作用可被去内皮或用L-NAME（内皮型一氧化氮合酶抑制剂）或化合物C（AMP活化蛋白激酶抑制剂）预处理的血管环所抑制。此外，KLX在培养的人脐静脉内皮细胞（HUVECs）中增加一氧化氮（NO）产生、内皮一氧化氮合酶（eNOS）、AKT和AMP活化蛋白激酶（AMPK）磷酸化，而这些作用被化合物C预处理细胞抑制。结论：KLX是一种具有降血压药理作用的新化合物。其机制与KLX通过激活AMPK-AKT-eNOS信号通路诱导内皮依赖性血管舒张有关。
Hypertension is a major risk factor for stroke and cardiovascular events in clinic, which is accompanied by the abnormality of vascular tone and endothelial dysfunction of small artery. Here we report that Kang Le Xin (KLX), a novel anthraquinones compound, could reduce blood pressure and the underlying mechanisms involves that KLX induces endothelium-dependent vasodilation. KLX significantly decreases the arterial blood pressure of spontaneous hypertensive rats (SHR), decreases the contractile reactivity of superior mesenteric artery to phenylephrine and increases the vasodilatory reactivity of superior mesenteric artery to carbachol in a dose-dependent manner. Besides, KLX reduces vascular tension of endothelium-intact mesenteric artery pre-constricted with phenylephrine in a dose-dependent manner, while this effect is inhibited by depriving vascular endothelium or pretreating vascular rings with L-NAME (endothelial nitric oxide synthase inhibitor) or compound C (AMP-activated protein kinase inhibitor). Moreover, KLX increases nitric oxide (NO) generation, endothelial nitric oxide synthase (eNOS), AKT and AMP-activated protein kinase (AMPK) phosphorylation in cultured human umbilical vein endothelial cells (HUVECs), while these effects are inhibited by pretreating cells with compound C. In conclusion, KLX is a new compound with the pharmacological action of reducing arterial blood pressure. The underlying mechanism involves KLX induces endothelium-dependent vasodilation through activating AMPK-AKT-eNOS signaling pathway.
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影响因子：
4
作者：
Ning, Wen-hu;Zhao, Kan
通讯作者：
Zhao, Kan
DOI：
10.1161/hypertensionaha.114.04683
发表时间：
2015-04
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Marina N;Ang R;Machhada A;Kasymov V;Karagiannis A;Hosford PS;Mosienko V;Teschemacher AG;Vihko P;Paton JF;Kasparov S;Gourine AV
通讯作者：
Gourine AV
影响因子：
4
作者：
RUBANYI, GM
通讯作者：
RUBANYI, GM
DOI：
10.1152/ajpheart.00377.2013
发表时间：
2013-12
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Peter Toth;A. Csiszar;Zsuzsanna Tucsek;D. Sosnowska;Tripti Gautam;A. Koller;M. Schwartzman;W. Sonntag-W.
通讯作者：
Peter Toth;A. Csiszar;Zsuzsanna Tucsek;D. Sosnowska;Tripti Gautam;A. Koller;M. Schwartzman;W. Sonntag-W.
DOI：
10.1161/atvbaha.108.179663
发表时间：
2009-06-01
影响因子：
8.7
作者：
Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone