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Renal sympathetic nerve activity regulates cardiovascular energy expenditure in rats fed high salt

Hypertension Research volume 43, pages 482–491 (2020)Cite this article

Abstract

We recently reported that a 4% high-salt diet + saline for drinking (HS + saline) leads to a catabolic state, reduced heart rate, and suppression of cardiovascular energy expenditure in mice. We suggested that HS + saline reduces heart rate via the suppression of the sympathetic nervous system to compensate for the high salt intake-induced catabolic state. To test this hypothesis, we directly measured renal sympathetic nerve activity (RSNA) in conscious Sprague-Dawley (SD) rats using a radiotelemetry system. We confirmed that HS + saline induced a catabolic state. HS + saline decreased heart rate, while also reducing RSNA in SD rats. In contrast, Dahl salt-sensitive (DSS) rats exhibited no change in heart rate and increased RSNA during high salt intake. Renal denervation significantly decreased heart rate and attenuated the catabolic state independent of blood pressure in DSS rats fed HS + saline, suggesting that salt-sensitive animals were unable to decrease cardiovascular energy consumption due to abnormal renal sympathetic nerve activation during high salt intake. These findings support the hypothesis that RSNA mediates heart rate during high salt intake in SD rats. However, the insensitivity of heart rate and enhanced RSNA observed in DSS rats may be additional critical diagnostic factors for salt-sensitive hypertension. Renal denervation may benefit salt-sensitive hypertension by reducing its effects on catabolism and cardiovascular energy expenditure.

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Acknowledgements

This study was partially supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI: 18H03191) and the Salt Sciences Foundation (18C5) to AN. We are deeply grateful to Mr. Masao Masui and Ms. Sachiko Okegawa (Osaka General City Hospital) for animal maintenance at Osaka General City Hospital.

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Authors and Affiliations

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

    Norihiko Morisawa, Kento Kitada, Daisuke Nakano, Daisuke Yamazaki, Lei Li, Yifan Zhang & Akira Nishiyama

  2. Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Norihiko Morisawa & Takashi Yokoo

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

    Kento Kitada & Jens Titze

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

    Yoshihide Fujisawa

  5. Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan

    Daisuke Yamazaki, Takashi Morikawa & Yoshio Konishi

  6. Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan

    Shuhei Kobuchi

  7. Experimental & Clinical Research Center, a joint collaboration between Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin, Berlin, Germany

    Friedrich C. Luft

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

    Jens Titze

  9. Division of Nephrology and Hypertension, University Clinic Erlangen, Erlangen, Germany

    Jens Titze

Authors
  1. Norihiko Morisawa
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Contributions

NM, KK, YF, DY, LL, YZ, and TM performed the animal experiments. KK, TM, YK, TY, JT, and AN provided essential material and contributed to the design of the experiments. SK measured, analyzed, and interpreted the tissue noradrenaline content data. NM and YF performed animal surgery and radiotelemetry measurements. NM, KK, and YF analyzed the radiotelemetry data. NM, KK, DN, DY, JT, and AN designed and planned the experiments and analyzed and interpreted the data. NM, KK, DN, FL, JT, and AN wrote the paper. YK, TY, FL, JT, and AN supervised the research project.

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Correspondence to Kento Kitada.

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Morisawa, N., Kitada, K., Fujisawa, Y. et al. Renal sympathetic nerve activity regulates cardiovascular energy expenditure in rats fed high salt. Hypertens Res 43, 482–491 (2020). https://doi.org/10.1038/s41440-019-0389-1

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