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Contribution of afferent renal nerve signals to acute and chronic blood pressure regulation in stroke-prone spontaneously hypertensive rats

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  • ISH2022–Fast track: Renal Denervation
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Abstract

The activation of sympathetic nervous system plays a critical role in the development of hypertension. The input from afferent renal nerves may affect central sympathetic outflow; however, its contribution to the development of hypertension remains unclear. We investigated the role of afferent renal nerves in acute and chronic blood pressure regulation using normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acute chemical stimulation of afferent renal nerves elicited larger increases in blood pressure and renal sympathetic nerve activity in young 9-week-old SHRSP compared to WKY. Selective afferent renal denervation (ARDN) and conventional total renal denervation (TRDN) ablating both afferent and efferent nerves in young SHRSP revealed that only TRDN, but not ARDN, chronically attenuated blood pressure elevation. ARDN did not affect plasma renin activity or plasma angiotensin II levels, whereas TRDN decreased both. Neither TRDN nor ARDN affected central sympathetic outflow and systemic sympathetic activity determined by neuronal activity in the parvocellular region of hypothalamic paraventricular nucleus and rostral ventrolateral medulla and by plasma and urinary norepinephrine levels, respectively. Renal injury was not apparent in young SHRSP compared with WKY, suggesting that renal afferent input might not be activated in young SHRSP. In conclusion, the chronic input from afferent renal nerves does not contribute to the development of hypertension in SHRSP despite the increased blood pressure response to the acute stimulation of afferent renal nerves. Efferent renal nerves may be involved in the development of hypertension via activation of the renin-angiotensin system in SHRSP.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number JP21K08032 (KS).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shota Ikeda, Keisuke Shinohara, Soichiro Kashihara, Sho Matsumoto, Daisuke Yoshida, Ryosuke Nakashima, Yoshiyasu Ono, Masaaki Nishihara & Hiroyuki Tsutsui

  2. Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shota Ikeda, Keisuke Shinohara, Soichiro Kashihara, Sho Matsumoto, Daisuke Yoshida, Ryosuke Nakashima, Yoshiyasu Ono & Hiroyuki Tsutsui

  3. Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan

    Masaaki Nishihara

  4. Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan

    Kenichi Katsurada

  5. Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University School of Medicine, Tochigi, Japan

    Kenichi Katsurada

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  1. Shota Ikeda
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Correspondence to Keisuke Shinohara.

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KS reports grants from Daiichi Sankyo, Nippon Boehringer Ingelheim, and Otsuka Medical Devices. HT reports grants and/or personal fees from Daiichi Sankyo, Novartis Pharma, Otsuka Pharmaceutical, Pfizer Japan, Mitsubishi Tanabe Pharma, Teijin Pharma, Nippon Boehringer Ingelheim, AstraZeneca, Ono Pharmaceutical, Kowa, IQVIA Service Japan, MEDINET, Medical Innovation Kyushu, Bayer Yakuhin, Johnson & Johnson, NEC, Nippon Rinsho and Japanese Heart Failure Society. Other authors report no conflicts of interest.

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Ikeda, S., Shinohara, K., Kashihara, S. et al. Contribution of afferent renal nerve signals to acute and chronic blood pressure regulation in stroke-prone spontaneously hypertensive rats. Hypertens Res 46, 268–279 (2023). https://doi.org/10.1038/s41440-022-01091-z

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