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Effects of an SGLT2 inhibitor on the salt sensitivity of blood pressure and sympathetic nerve activity in a nondiabetic rat model of chronic kidney disease

Hypertension Research volume 43, pages 492–499 (2020)Cite this article

Abstract

The glucose-lowering effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors is reduced in patients with diabetes who have chronic kidney disease (CKD). In the present study, we examined the effect of an SGLT2 inhibitor on the salt sensitivity of blood pressure (BP), circadian rhythm of BP, and sympathetic nerve activity (SNA) in nondiabetic CKD rats. Uninephrectomized Wistar rats were treated with adenine (200 mg/kg/day) for 14 days. After stabilization with a normal-salt diet (NSD, 0.3% NaCl), a high-salt diet (HSD, 8% NaCl) was administered. Mean arterial pressure (MAP) was continuously monitored using a telemetry system. We also analyzed the low frequency (LF) of systolic arterial pressure (SAP), which reflects SNA. In adenine-induced CKD rats, HSD consumption for 5 days significantly increased the mean MAP from 106 ± 2 to 148 ± 3 mmHg. However, MAP was decreased to 96 ± 3 mmHg within 24 h after switching back to a NSD (n = 7). Treatment with an SGLT2 inhibitor, luseogliflozin (10 mg/kg/day, p.o., n = 7), significantly attenuated the HSD-induced elevation of MAP, which was associated with a reduction in LF of SAP. These data suggest that treatment with an SGLT2 inhibitor attenuates the salt sensitivity of BP, which is associated with SNA inhibition in nondiabetic CKD rats.

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Acknowledgements

We thank Clare Cox, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This study was partly a collaboration with Taisho Co., Ltd. (through A.N.). This work was also supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) and the Salt Sciences Foundation (to AN). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

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

    Ningning Wan, Daisuke Nakano, Asadur Rahman & Akira Nishiyama

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

    Yoshihide Fujisawa

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

    Hideki Kobara & Tsutomu Masaki

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  1. Ningning Wan
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Contributions

This study was performed at Kagawa University. All authors were involved in the acquisition, analysis, or interpretation of data. AN was involved in the conception and design of the study. NW wrote the manuscript, and AR and AN revised it critically for important intellectual content. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All people designated as authors qualify for authorship.

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Correspondence to Akira Nishiyama.

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AN has received honoraria for educational meetings conducted on behalf of Taisho Co., Ltd. The authors declare that there are no other conflicts of interest.

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Wan, N., Fujisawa, Y., Kobara, H. et al. Effects of an SGLT2 inhibitor on the salt sensitivity of blood pressure and sympathetic nerve activity in a nondiabetic rat model of chronic kidney disease. Hypertens Res 43, 492–499 (2020). https://doi.org/10.1038/s41440-020-0410-8

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