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Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats

Hypertension Research volume 46, pages 32–39 (2023)Cite this article

Abstract

We recently reported that skin vasoconstriction to suppress transepidermal water loss (TEWL) leads to hypertension in renal injury model rats with impaired urine concentration ability. In this study, we investigated the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs) from the perspective of renal water loss and skin water conservation. We compared the urinary concentration ability, body sodium and water balance, blood pressure, and TEWL in SHRs and control normotensive Wistar–Kyoto rats (WKYs). SHRs showed significantly higher urine volume and lower urinary osmolality than those of WKYs, while there were no significant differences in water intake, urinary osmolyte excretion, and plasma osmolarity between the groups. SHRs exhibited significantly higher blood pressure, skin sodium content, and lower TEWL compared with those is WKYs. Skin vasodilation, induced by elevating body temperature, increased TEWL in both SHRs and WKYs, and significantly reduced blood pressure in SHRs but not WKYs. These findings suggest that physiological adaptation can reduce dermal water loss in SHRs to compensate for renal water loss. Vasoconstriction required for successful cutaneous water conservation explains SHR hypertension. Renal concentration ability and skin barrier function for water conservation may become a novel therapeutic target for essential hypertension.

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Acknowledgements

We thank Miho Yamauchi, Miyuki Namio, Kanoko Ueta, and Manami Shoji, technical assistants at Kagawa University. We also thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by Grants-in-Aid for Scientific Research (22H03514 to AN) and the Uehara Memorial Foundation (AN), and it was partially supported by Grants-in-Aid for Young Scientists (Start-up) (20K22876 to KK), the MSD Life Science Foundation (KK), and the Astellas Foundation for Research on Metabolic Disorders (KK).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Kagawa University, 7610793, Kagawa, Japan

    Takahiro Ogura, Kento Kitada, Satoshi Kidoguchi, Daisuke Nakano & Akira Nishiyama

  2. Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 169857, Singapore, Singapore

    Norihiko Morisawa & Jens Titze

  3. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 1058461, Tokyo, Japan

    Norihiko Morisawa & Satoshi Kidoguchi

  4. Life Science Research Center, Faculty of Medicine, Kagawa University, 7610793, Kagawa, Japan

    Yoshihide Fujisawa

  5. Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 7610793, Kagawa, Japan

    Hideki Kobara & Tsutomu Masaki

  6. Division of Nephrology and Hypertension, Friedrich-Alexander University Erlangen-Nuremberg, 91054, Erlangen, Germany

    Jens Titze

  7. Division of Nephrology, Duke University Medical Center, Durham, NC, 27705, USA

    Jens Titze

Authors
  1. Takahiro Ogura
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  2. Kento Kitada
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  3. Norihiko Morisawa
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  10. Akira Nishiyama
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Contributions

Conceptualization, KK, and JT; Methodology, TO, KK, NM, YF, and JT; Software, KK; Validation, TO, KK, YF, NM, SK, DN, HK, TM, JT, and AN; Formal Analysis, TO and KK; Investigation, TO, KK, NM, YF, and SK; Resources, KK, DN, HK, TM, JT, and AN; Data Curation, TO, KK, NM, YF, and SK; Writing - Original Draft Preparation, TO and KK; Writing - Review & Editing, TO, KK, SK, DN, HK, TM, JT, and AN; Visualization, TO and KK; Supervision, KK, DN, JT, and AN; Project Administration, KK, DN, JT, and AN; Funding Acquisition, KK and AN.

Corresponding author

Correspondence to Kento Kitada.

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The authors declare no competing interests.

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The animal research committee of Kagawa University reviewed and approved animal experiments.

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Ogura, T., Kitada, K., Morisawa, N. et al. Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats. Hypertens Res 46, 32–39 (2023). https://doi.org/10.1038/s41440-022-01044-6

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