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Original Article

Korean J Physiol Pharmacol 2023; 27(3): 209-220

Published online May 1, 2023

Copyright © Korean J Physiol Pharmacol.

Edaravone alleviates lung damage in mice with hypoxic pulmonary hypertension by increasing nitric oxide synthase 3 expression

Wan Zheng*, Tianfa Li, Junping Wei, Yani Yan, and Shanshan Yang

Department of Cardiovascular Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China

Correspondence to:Wan Zheng

Author contributions: W.Z. conceived the ideas. W.Z. and T.F.L. designed the experiments. W.Z., T.F.L., and J.P.W. performed the experiments. W.Z., T.F.L., and Y.N.Y. analyzed the data. W.Z. and T.F.L. provided critical materials. W.Z. and S.S.Y. wrote the manuscript. All the authors have read and approved the final version for publication.

Received: June 8, 2022; Revised: August 2, 2022; Accepted: August 2, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


This study is to determine the regulation of nitric oxide synthase 3 (NOS3) by edaravone in mice with hypoxic pulmonary hypertension (HPH). C57BL/6J mice were reared in a hypoxic chamber. HPH mice were treated with edaravone or edaravone + L-NMMA (a NOS inhibitor). Lung tissue was collected for histological assessment, apoptosis analysis, and detection of malondialdehyde, superoxide dismutase, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and NOS3. The levels of serum TNF-α and IL-6 were also measured. Immunohistochemistry was used to visualize the expression of α-smooth muscle actin (SMA) in pulmonary arterioles. Edaravone treatment improved hemodynamics, inhibited right ventricular hypertrophy, increased NOS3 expression, and reduced pathological changes, pulmonary artery wall thickness, apoptotic pulmonary cells, oxidative stress, and the expression of TNF-α, IL-6, and α-SMA in HPH mice. L-NMMA treatment counteracted the lung protective effects of edaravone. In conclusion, edaravone might reduce lung damage in HPH mice by increasing the expression of NOS3.

Keywords: Edaravone, Hypertension, pulmonary, Lung injury, Nitric oxide synthase