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SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats

Hypertension Research volume 47, pages 46–54 (2024)Cite this article

Abstract

Hypertension is well-known to often coexist with diabetes mellitus (DM) in humans. Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors has been shown to decrease both the blood glucose and the blood pressure (BP) in such patients. Some reports show that SGLT2 inhibitors improve the BP by decreasing the activities of the sympathetic nervous system. Therefore, we hypothesized that SGLT2 inhibitors might alleviate hypertension via attenuating sympathetic nervous activity. Combined SGLT2/SGLT1 inhibitor therapy is also reported as being rather effective for decreasing the BP. In this study, we examined the effects of SGLT2 and SGLT1 inhibitors on the bulbospinal neurons of the rostral ventrolateral medulla (RVLM). To investigate whether bulbospinal RVLM neurons are sensitive to SGLT2 and SGLT1 inhibitors, we examined the changes in the neuronal membrane potentials (MPs) of these neurons using the whole-cell patch-clamp technique during superfusion of the cells with the SGLT2 and SGLT1 inhibitors. A brainstem–spinal cord preparation was used for the experiments. Our results showed that superfusion of the RVLM neurons with SGLT2 and SGLT1 inhibitor solutions induced hyperpolarization of the neurons. Histological examination revealed the presence of SGLT2s and SGLT1s in the RVLM neurons, and also colocalization of SGLT2s with SGLT1s. These results suggest the involvement of SGLT2s and SGLT1s in regulating the activities of the RVLM neurons, so that SGLT2 and SGLT1 inhibitors may inactivate the RVLM neurons hyperpolarized by empagliflozin.

SGLT2 and SGLT1 inhibitors suppressed the activities of the bulbospinal RVLM neurons in the brainstem-spinal preparations, suggesting the possibilities of lowering BP by decreasing the sympathetic nerve activities. RVLM, rostral ventrolateral medulla. IML, intralateral cell column. aCSF, artificial cerebrospinal fluid.

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Authors and Affiliations

  1. Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Saitama, Japan

    Naoki Oshima, Aoi Yamashiro, Hiroyasu Goto, Keiko Tanoue, Tsugumi Fukunaga, Hiroki Sato, Asuka Uto, Hidehito Matsubara & Toshihiko Imakiire

  2. Department of Physiology, Showa University School of Medicine, Tokyo, Japan

    Hiroshi Onimaru

  3. Department of Nephrology, Sayama General Clinic, Iruma, Saitama, Japan

    Hiroo Kumagai

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  1. Naoki Oshima
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Correspondence to Naoki Oshima.

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Oshima, N., Onimaru, H., Yamashiro, A. et al. SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats. Hypertens Res 47, 46–54 (2024). https://doi.org/10.1038/s41440-023-01417-5

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