Artemisinin Improves Acetylcholine-Induced Vasodilatation in Rats with Primary Hypertension

Abstract

Purpose

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.

Graphical Abstract

Keywords:

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

Abbreviations

ACh, acetylcholine; CA, coronary artery; eNOS, endothelial nitric oxide synthase; MA, mesenteric artery; NO, nitric oxide; PA, pulmonary artery; ROS, reactive oxygen species; SHR, spontaneously hypertensive rat; WKY, Wistar-Kyoto rat.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author Ying Han upon reasonable request.

Ethical Approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All animal procedures were reviewed and approved by Nanjing Medical University Experimental Animal Care committee and in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication, 8th edition, 2011).

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was sponsored by the National Natural Science Foundation of China [81470538, 81970052 and 82170057], Qing Lan Project of Jiangsu Province of China and the Open Project of the State Key Laboratory of Respiratory Disease (SKLRD-OP-201911).