Key Laboratory of Targeted Intervention for Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Department of Physiology and Pathologic Physiology, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People's Republic of China.
Drug Des Devel Ther. 2021 Nov 2;15:4489-4502. doi: 10.2147/DDDT.S330721. eCollection 2021.
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.
内皮功能障碍及随之而来的小动脉内皮依赖性血管舒张功能下降是高血压的主要特征。青蒿素作为一种著名的抗疟药物，已被证明在心脏和肺血管疾病中对内皮细胞损伤具有保护作用。本研究旨在探讨青蒿素对自发性高血压大鼠（SHR）内皮依赖性血管舒张和动脉血压的影响及其潜在的信号通路。
本研究采用乙酰胆碱（ACh）诱导的剂量依赖性舒张试验，评价青蒿素处理后血管内皮功能。通过静脉注射或孵育将青蒿素用于急性暴露实验中的大鼠，通过腹腔注射将青蒿素用于慢性实验中的大鼠。
急性和慢性给予青蒿素均可降低心率，改善 ACh 诱导的内皮依赖性舒张，但对 SHR 的动脉血压影响不大。青蒿素孵育可降低肠系膜动脉、冠状动脉和肺动脉的基础血管张力、NAD（P）H 氧化酶活性和活性氧（ROS）水平，但也可增加内皮型一氧化氮合酶（eNOS）活性和 NO 水平。青蒿素慢性给予 SHR 可增加肠系膜动脉中 eNOS 的蛋白表达，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，青蒿素治疗可降低心率和基础血管张力，改善高血压患者的内皮依赖性血管舒张功能，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。
