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Effects of bilateral renal denervation on open-loop baroreflex function and urine excretion in spontaneously hypertensive rats

Hypertension Research (2024)Cite this article

Abstract

Bilateral renal denervation (RDN) decreases arterial pressure (AP) or delays the development of hypertension in spontaneously hypertensive rats (SHR), but whether bilateral RDN significantly modifies urine output function during baroreflex-mediated acute AP changes remains unknown. We quantified the relationship between AP and normalized urine flow (nUF) in SHR that underwent bilateral RDN (n = 9) and compared the results with those in sham-operated SHR (n = 9). Moreover, we examined the acute effect of an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) on the AP–nUF relationship. Bilateral RDN significantly decreased AP by narrowing the response range of the total arc of the carotid sinus baroreflex. The slopes of nUF versus the mean AP (in μL·min−1·kg−1·mmHg−1) in the sham and RDN groups under baseline conditions were 0.076 ± 0.045 and 0.188 ± 0.039, respectively; and those after telmisartan administration were 0.285 ± 0.034 and 0.416 ± 0.078, respectively. The effect of RDN on the nUF slope was marginally significant (P = 0.059), which may have improved the controllability of urine output in the RDN group. The effect of telmisartan on the nUF slope was significant (P < 0.001) in the sham and RDN groups, signifying the contribution of circulating or locally produced angiotensin II to determining urine output function regardless of ongoing renal sympathetic nerve activity.

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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

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Funding

This study was partly supported by the research program of the Japan Agency for Medical Research and Development (24ama121050j0003), the research program of the Ministry of Internal Affairs and Communications (SCOPE: JP225006004), the Grant-in-Aid for Scientific Research (22K08222, 23K08449, 24K19018), the research grant from the Salt and Science Research Foundation (2125), the research grant from JST (JPMJPF2018), and the research grant from NTT Research, Inc. The authors confirm that these parties did not influence the study design, contents of the article, or selection of this journal.

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Authors and Affiliations

  1. Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan

    Toru Kawada, Masafumi Fukumitsu, Hiroki Matsushita, Yuki Yoshida, Kei Sato, Hidetaka Morita & Keita Saku

  2. Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, Osaka, Japan

    Takuya Nishikawa

  3. Corporate R&D Center, Terumo Corporation, Kanagawa, Japan

    Satoru Suehara & Satoshi Sawada

  4. Bio Digital Twin Center, National Cerebral and Cardiovascular Center, Osaka, Japan

    Keita Saku

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  1. Toru Kawada
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Contributions

Toru Kawada and Keita Saku conceived and designed the study. Toru Kawada performed the experiments and analyzed data. Toru Kawada, Masafumi Fukumitsu, Hiroki Matsushita, Yuki Yoshida, Kei Sato, Hidetaka Morita, Takuya Nishikawa, Satoru Suehara, Satoshi Sawada, and Keita Saku discussed and interpreted the results of the experiments. Toru Kawada prepared the figures and drafted the manuscript. Toru Kawada and Keita Saku edited and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Toru Kawada.

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Conflict of interest

Toru Kawada received a consulting fee from NTT Research, Inc. Keita Saku received research funding from Abiomed Japan K.K., NTT Research, Inc., Asahi Kasei ZOLL Medical Corporation, Neuroceuticals, Inc., and Zeon Medical, Inc., and honoraria from Abiomed Japan K.K. and Mallinckrodt Pharmaceuticals, Inc. Other authors declare no conflict of interest.

Consent to participate

This study did not involve human participants. The Animal Subject Committee at the National Cerebral and Cardiovascular Center has approved the animal experiments.

Ethics approval

Male SHR, purchased from Japan SLC, were cared for in strict compliance with the Guiding Principles for the Care and Use of Animals in the Field of Physiological Sciences, which the Physiological Society of Japan has approved. The Animal Subjects Committee at the National Cerebral and Cardiovascular Center reviewed and approved all experimental protocols (21009, 22033, 23013).

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Kawada, T., Fukumitsu, M., Matsushita, H. et al. Effects of bilateral renal denervation on open-loop baroreflex function and urine excretion in spontaneously hypertensive rats. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01883-5

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