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Upregulation of Nav1.6 expression in the rostral ventrolateral medulla of stress-induced hypertensive rats

Hypertension Research volume 41, pages 1013–1022 (2018)Cite this article

Abstract

The rostral ventrolateral medulla (RVLM) plays a key role in mediating the development of stress-induced hypertension (SIH) by excitation and/or inhibition of sympathetic preganglionic neurons. The voltage-gated sodium channel Nav1.6 has been found to contribute to neuronal hyperexcitability. To examine the expression of Nav1.6 in the RVLM during SIH, a rat model was established by administering electric foot-shocks and noises. We found that Nav1.6 protein expression in the RVLM of SIH rats was higher than that of control rats, peaking at the tenth day of stress. Furthermore, we observed changes in blood pressure correlating with days of stress, with systolic blood pressure (SBP) found to reach a similarly timed peak at the tenth day of stress. Percentages of cells exhibiting colocalization of Nav1.6 with NeuN, a molecular marker of neurons, indicated a strong correlation between upregulation of Nav1.6 expression in NeuN-positive cells and SBP. The level of RSNA was significantly increased after 10 days of stress induction than control group. Compared with the SIHR, knockdown of Nav1.6 in RVLM of the SIHR decreased the level of SBP, heart rate (HR) and renal sympathetic nerve activity (RSNA). These results suggest that upregulated Nav1.6 expression within neurons in the RVLM of SIH rats may contribute to overactivation of the sympathetic system in response to SIH development.

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Acknowledgements

The present study was supported by the Chinese National Natural Science Foundation (grant nos. 31871151, 31571171, and 31100838), the Key Laboratory of Medical Electrophysiology (Southwest Medical University) of Ministry of Education of China (grant no. 201502) and the Young Teachers of Shanghai Universities Training Program.

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Author notes

  1. These authors contributed equally: Jia-Xiang Wu, Lei Tong, Li Hu

Affiliations

  1. Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai University, Shanghai, China

    Jia-Xiang Wu, Lei Tong, Li Hu, Chun-Mei Xia, Min Li, Fu-Xue Chen & Dong-Shu Du

  2. Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai, China

    Chun-Mei Xia

  3. Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA

    Qing-Hui Chen

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  1. Jia-Xiang Wu
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Correspondence to Dong-Shu Du.

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Wu, JX., Tong, L., Hu, L. et al. Upregulation of Nav1.6 expression in the rostral ventrolateral medulla of stress-induced hypertensive rats. Hypertens Res 41, 1013–1022 (2018). https://doi.org/10.1038/s41440-018-0105-6

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  • DOI: https://doi.org/10.1038/s41440-018-0105-6

Keywords:

  • Stress
  • Hypertension
  • Nav1.6
  • RVLM
  • Neuron

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