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Aortic smooth muscle TRPV4 channels regulate vasoconstriction in high salt-induced hypertension

Hypertension Research volume 46, pages 2356–2367 (2023)Cite this article

A Comment to this article was published on 17 August 2023

Abstract

Recent studies have focused on the contribution of vascular endothelial transient receptor potential vanilloid 4 (TRPV4) channels to hypertension. However, in hypertension, TRPV4 channels in vascular smooth muscle remain unexplored. In the present study, we performed wire myograph experiments in isolated aortas from endothelial cell specific TRPV4 channel knockout (TRPV4EC−/−) mice to demonstrate that GSK1016790A (a specific TRPV4 channel agonist) triggered aortic smooth muscle-dependent contractions from mice on a normal-salt diet, and the contractions were enhanced in high-salt diet (HSD) mice. Intracellular Ca2+ concentration ([Ca2+]i) and Ca2+ imaging assays showed that TRPV4-induced [Ca2+]i was significantly higher in aortic smooth muscle cells (ASMCs) from HSD-induced hypertensive mice, and application of an inositol trisphosphate receptor (IP3R) inhibitor markedly attenuated TRPV4-induced [Ca2+]i. IP3R2 expression was enhanced in ASMCs from HSD-induced hypertensive mice and the contractile response induced by TRPV4 was inhibited by the IP3R inhibitor. Whole-transcriptome analysis by RNA-seq and western blot assays revealed the involvement of interferon regulatory factor 7 (IRF7) in TRPV4–IRF7–IP3R2 signaling in HSD-induced hypertension. These results suggested that TRPV4 channels regulate smooth muscle-dependent contractions in high salt-induced hypertension, and this contraction involves increased [Ca2+]i, IP3R2, and IRF7 activity. Our study revealed a considerable effect of TRPV4 channels in smooth muscle-dependent contraction in mice during high-salt induced hypertension.

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Data availability

The data sets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Prof. Iain C. Bruce for critical reading of the article.

Funding

This work was supported by the National Natural Science Foundation of China [81970397 and 82200463], the Postdoctoral Research funding program of Jiangsu Province [2020Z427], and the Wuxi Health Commission [2020ZHZD02].

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  1. These authors contributed equally: Xin Wen, Yidi Peng

Authors and Affiliations

  1. Wuxi School of Medicine, Jiangnan University, Wuxi, 214000, China

    Xin Wen, Yuefeng Peng, Yuzhong Zhu, Fan Yu, Li Geng, Tingting Zhou, Xianfeng Wang & Lei Feng

  2. School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214000, China

    Yidi Peng

  3. Department of Vascular Surgery, General Surgery Clinical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Qingyou Meng

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Contributions

XW and QM designed the research. XW, YDP, YZZ, and FY performed the whole-transcriptome analysis by RNA-seq and western blot assays and analysis. YFP, XFW, and LG did the wire myograph experiments. YFP, TZ, XW, and LF did the [Ca2+]i and Ca2+ imaging assays. XW wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Qingyou Meng.

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Wen, X., Peng, Y., Peng, Y. et al. Aortic smooth muscle TRPV4 channels regulate vasoconstriction in high salt-induced hypertension. Hypertens Res 46, 2356–2367 (2023). https://doi.org/10.1038/s41440-023-01363-2

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