Artemisinin Improves Acetylcholine-Induced Vasodilatation in Rats with Primary Hypertension.
Artemisinin Improves Acetylcholine-Induced Vasodilatation in Rats with Primary Hypertension.
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DOI：
10.2147/dddt.s330721
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Han Y
中科院分区：
文献类型：
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作者：
Liu X;Wang X;Pan Y;Zhao L;Sun S;Luo A;Bao C;Tang H;Han Y
内皮功能障碍和随后小动脉内皮依赖性血管舒张的减少是高血压的主要特征。青蒿素是一种著名的抗疟药，已被证明在心脏和肺血管疾病中发挥针对内皮细胞损伤的保护作用。本研究旨在探讨青蒿素对内皮依赖性血管舒张和动脉血压的影响，以及自发性高血压大鼠（SHR）中潜在的信号通路。在这项研究中，进行了乙酰胆碱（ACh）诱导的剂量依赖性舒张试验，以评估青蒿素治疗后的血管内皮功能。急性暴露实验采用静脉注射青蒿素或动脉温育给药方式，慢性暴露实验采用腹腔注射青蒿素28 d。急性和长期服用青蒿素均可降低心率并改善乙酰胆碱诱导的内皮依赖性舒张，但对 SHR 的动脉血压影响可忽略不计。青蒿素孵育降低了基础血管张力、NAD(P)H氧化酶活性和活性氧(ROS)水平，但也增加了SHR的肠系膜动脉、冠状动脉和肺动脉中的内皮一氧化氮(NO)合酶(eNOS)活性和NO水平。长期给予 SHR 青蒿素可增加肠系膜动脉中 eNOS 的蛋白表达，并降低 NAD(P)H 氧化酶亚基 NOX-2 和 NOX-4 的蛋白表达。这些结果表明，青蒿素治疗对降低心率和基础血管张力以及改善高血压患者的内皮依赖性血管舒张具有有益作用，这可能是通过增加 eNOS 激活和 NO 释放以及抑制 NAD(P)H 氧化酶衍生的 ROS 产生来实现的。
Endothelial dysfunction and the subsequent decrease in endothelium-dependent vascular relaxation of small arteries are major features of hypertension. Artemisinin, a well-known antimalarial drug, has been shown to exert protecting roles against endothelial cell injury in cardiac and pulmonary vascular diseases. The current study aimed to investigate the effects of artemisinin on endothelium-dependent vascular relaxation and arterial blood pressure, as well as the potential signalling pathways in spontaneously hypertensive rats (SHRs). In this study, acetylcholine (ACh)-induced dose-dependent relaxation assays were performed to evaluate vascular endothelial function after treatment with artemisinin. Artemisinin was administered to the rats by intravenous injection or to arteries by incubation for the acute exposure experiments, and it was administered to rats by intraperitoneal injection for 28 days for the chronic experiments. Both acute and chronic administration of artemisinin decreased the heart rate and improved ACh-induced endothelium-dependent relaxation but negligibly affected the arterial blood pressure in SHRs. Incubation with artemisinin decreased basal vascular tension, NAD(P)H oxidase activity and reactive oxygen species (ROS) levels, but it also increased endothelial nitric oxide (NO) synthase (eNOS) activity and NO levels in the mesenteric artery, coronary artery, and pulmonary artery of SHRs. Artemisinin chronic administration to SHRs increased the protein expression of eNOS and decreased the protein expression of the NAD(P)H oxidase subunits NOX-2 and NOX-4 in the mesenteric artery. These results indicate that treatment with artemisinin has beneficial effects on reducing the heart rate and basal vascular tension and improving endothelium-dependent vascular relaxation in hypertension, which might occur by increasing eNOS activation and NO release and inhibiting NAD(P)H oxidase derived ROS production.