Artemisinin Improves Acetylcholine-Induced Vasodilatation in Rats with Primary Hypertension

Abstract

Xuanxuan Liu,1,2 Xingxing Wang,1 Yan Pan,1 Li Zhao,3 Shuo Sun,1 Ang Luo,3 Changlei Bao,3,4 Haiyang Tang,3,4 Ying Han1 1Key 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; 2Department of Physiology and Pathologic Physiology, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China; 3College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Ying HanKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of ChinaTel/Fax [phone]Email [email protected] TangState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of ChinaTel [phone]Email [email protected]: 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).Methods: 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.Results: 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.Conclusion: 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.Keywords: hypertension, artemisinin, vascular function, nitric oxide, reactive oxygen species

Keywords

• hypertension
• artemisinin
• vascular function
• nitric oxide
• reactive oxygen species