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Review Series – New Horizons in the Treatment of Hypertension

Renal denervation based on experimental rationale

Hypertension Research volume 44, pages 1385–1394 (2021)Cite this article

Abstract

Excessive activation of the sympathetic nervous system is one of the pathophysiological hallmarks of hypertension and heart failure. Within the central nervous system, the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla in the brain stem play critical roles in the regulation of sympathetic outflow to peripheral organs. Information from the peripheral circulation, including serum concentrations of sodium and angiotensin II, is conveyed to the PVN via adjacent structures with a weak blood–brain barrier. In addition, signals from baroreceptors, chemoreceptors and cardiopulmonary receptors as well as afferent input via the renal nerves are all integrated at the level of the PVN. The brain renin-angiotensin system and the balance between nitric oxide and reactive oxygen species in these brain areas also determine the final sympathetic outflow. Additionally, brain inflammatory responses have been shown to modulate these processes. Renal denervation interrupts both the afferent inputs from the kidney to the PVN and the efferent outputs from the PVN to the kidney, resulting in the suppression of sympathetic outflow and eliciting beneficial effects on both hypertension and heart failure.

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Funding

This work was supported in part by National Institutes of Health grants R56 HL124104, P01 HL62222, and R01 DK114663; by an endowed McIntyre Professorship (to KPP); and by a Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad (to KKatsurada).

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan

    Kenichi Katsurada, Yukako Ogoyama, Yasushi Imai & Kazuomi Kario

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

    Kenichi Katsurada & Yasushi Imai

  3. Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA

    Kaushik P. Patel

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  1. Kenichi Katsurada
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Contributions

KKatsurada, YO, YI, KPP and KKario conducted the conception and design of the study. KKatsurada and KPP performed the study including experimental data collection and analyses. KKatsurada drafted the manuscript. KKatsurada, YO, YI, KPP and KKario edited and revised the manuscript.

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Correspondence to Kazuomi Kario.

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Kazuomi Kario MD PhD, received speaker fees and worked as a consultant to JIMRO Co. Ltd., Medtronic Co. Inc. and Terumo Co. Inc. The other authors declare no competing interests.

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Katsurada, K., Ogoyama, Y., Imai, Y. et al. Renal denervation based on experimental rationale. Hypertens Res 44, 1385–1394 (2021). https://doi.org/10.1038/s41440-021-00746-7

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