2. Academic Validation
  3. Resveratrol reduces RVLM neuron activity via activating the AMPK/Sirt3 pathway in stress-induced hypertension

Resveratrol reduces RVLM neuron activity via activating the AMPK/Sirt3 pathway in stress-induced hypertension

  • J Biol Chem. 2025 Mar 10:108394. doi: 10.1016/j.jbc.2025.108394.
Lin-Ping Wang 1,  Tian-Feng Liu 1,  Teng-Teng Dai 2,  Xin Deng 3,  Lei Tong 2,  Qiang-Cheng Zeng 4,  Qing He 4,  Zhang-Yan Ren 2,  Hai-Li Zhang 5,  Hai-Sheng Liu 5,  Yan-Fang Li 6,  Wen-Zhi Li 7,  Shuai Zhang 8,  Dong-Shu Du 9
Affiliations

Affiliations

  • 1 School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China; School of Life Sciences, Shanghai University, Shanghai, China.
  • 2 School of Life Sciences, Shanghai University, Shanghai, China.
  • 3 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institute of Biomedical Science, Fudan University, Shanghai, China.
  • 4 College of Life Sciences, Dezhou University, Dezhou, Shandong, China.
  • 5 College of Agriculture and Bioengineering, Heze University, Heze, Shandong, China.
  • 6 Department of Preventive Medicine, Heze Medical College, Heze, Shandong, China.
  • 7 Department of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: wenchihlee@sina.com.
  • 8 International Cooperation Laboratory of Molecular Medicine, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address: szhang@zcmu.edu.cn.
  • 9 School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China; School of Life Sciences, Shanghai University, Shanghai, China; College of Life Sciences, Dezhou University, Dezhou, Shandong, China; College of Agriculture and Bioengineering, Heze University, Heze, Shandong, China; Department of Preventive Medicine, Heze Medical College, Heze, Shandong, China; Shaoxing Institute of Shanghai University, Shaoxing, Zhejiang, China. Electronic address: dsdu@shu.edu.cn.
PMID: 40074082 DOI: 10.1016/j.jbc.2025.108394
Abstract

Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this using an SIH rat model exposed to electric foot shocks and noise stimulation for 15 days. Analysis of RVLM tissue revealed increased mitochondrial damage, oxidative stress, Apoptosis, and dysregulated Ferroptosis in SIH rats. RSV microinjection into the RVLM reduced blood pressure, sympathetic vascular tone, and neuronal excitability. Both in vivo and in vitro studies showed that RSV treatment alleviated mitochondrial oxidative stress, Apoptosis, and Ferroptosis through AMPK activation and subsequent SIRT3 upregulation. These therapeutic effects were blocked by either AMPK inhibition or SIRT3 knockdown. Our findings demonstrate that RSV attenuates SIH by activating the AMPK/SIRT3 pathway, thereby reducing RVLM oxidative stress and cell death.

Keywords

Apoptosis; Ferroptosis; Mitochondrial oxidative stress; RVLM; Reactive oxygen species.

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