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Reply to ‘Neuroendocrine regulatory effects of sex hormones on salt sensitivity of blood pressure’

Nature Reviews Cardiology volume 22, pages 690–691 (2025)Cite this article

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We appreciate the opportunity to reply to the points raised by M. Zhou et al. (Neuroendocrine regulatory effects of sex hormones on salt sensitivity of blood pressure. Nat. Rev. Cardiol. https://doi.org/10.1338/10.1038/s41569-025-01175-6 2025)1 on our Review (Masenga, S. K. et al. Salt sensitivity of blood pressure: mechanisms and sex-specific differences. Nat. Rev. Cardiol. https://doi.org/10.1038/s41569-025-01135-0 2025)2.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable channel expressed in endothelium and neurons. Evidence indicates that endothelial TRPV4 activation causes vasodilatation by increasing intracellular Ca2+ concentration, which triggers nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor pathways3. However, under certain conditions (such as strong agonism or in specific vascular beds), TRPV4 activation can paradoxically evoke vasoconstriction3. Therefore, reports of a ‘dual’ role are context dependent: mild TRPV4 activation produces net vasodilatation, whereas very high TRPV4 activity or TRPV4 activation in specific vessels can cause vasoconstriction. Importantly, TRPV4 activation (with 4α-phorbol 12,13-didecanoate (4α-PDD)) has been shown to acutely lower blood pressure in rats, and a high-salt diet augments this hypotensive effect4. In the latter study, rats receiving a high-salt diet expressed more TRPV4 and had a larger drop in blood pressure in response to TRPV4 agonism, suggesting that TRPV4 provides a compensatory vasodilatory response to salt loading4.

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References

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Acknowledgements

The authors are funded by the Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging of the National Institutes of Health grants R01HL144941 (A.K.), 2D43TW009744 (S.K.M. and A.K.), R21TW012635 (S.K.M. and A.K.), and American Heart Association award number 24IVPHA1297559 https://doi.org/10.58275/AHA.24IVPHA1297559.pc.gr.193866 (S.K.M. and A.K.). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or the American Heart Association.

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Authors and Affiliations

  1. Department of Cardiovascular Science and Metabolic Diseases, Livingstone Center for Prevention and Translational Science, Livingstone, Zambia

    Sepiso K. Masenga

  2. Department of Pathology, Mulungushi University, Livingstone, Zambia

    Sepiso K. Masenga

  3. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Sepiso K. Masenga & Annet Kirabo

  4. Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA

    Sepiso K. Masenga & Annet Kirabo

  5. Department of Physiological Sciences, Mulungushi University, Livingstone, Zambia

    Sepiso K. Masenga

  6. Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Nashville, TN, USA

    Annet Kirabo

  7. Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA

    Annet Kirabo

  8. Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA

    Annet Kirabo

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Correspondence to Annet Kirabo.

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Masenga, S.K., Kirabo, A. Reply to ‘Neuroendocrine regulatory effects of sex hormones on salt sensitivity of blood pressure’. Nat Rev Cardiol 22, 690–691 (2025). https://doi.org/10.1038/s41569-025-01176-5

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