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The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses

Hypertension Research volume 46, pages 456–467 (2023)Cite this article

A Comment to this article was published on 18 November 2022

Abstract

The aim of this study was to investigate alterations in the intrarenal blood pressure (BP) regulation system after renal denervation (RDN) guided by renal nerve stimulation (RNS). Twenty-one dogs were randomized to receive RDN at strong (SRA group, n = 7) or weak (WRA group, n = 7) BP-elevation response sites identified by RNS or underwent RNS only (RNS-control, RSC, n = 7). After 4 weeks of follow-up, renal sympathetic components, the main components of renin-angiotensin system (RAS) and the major transporters involved in sodium and water reabsorption were assessed by immunohistochemical analysis. Compared with RSC treatment, RDN therapy significantly reduced renal norepinephrine and tyrosine hydroxylase levels, decreased the renin content and inhibited the onsite generation of angiotensinogen. Moreover, the expression of exciting axis components, including angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II type-1 receptor, was downregulated, while protective axis components for the cardiovascular system, including ACE2 and Mas receptors, were upregulated in both WRA and SRA groups. Moreover, RDN reduced the abundance of aquaporin-1 and aquaporin-2 in kidneys. Although RDN had a minimal effect on overall NKCC2 expression, its activation (p-NKCC2) and directional enrichment in the apical membrane (mNKCC2) were dramatically blunted. All these changes were more obvious in the SRA group than WRA group. Selective RDN guided by RNS effectively reduced systemic BP by affecting the renal neurohormone system, as well as the sodium and water transporter system, and these effects at sites with a strong BP response were more superior.

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Acknowledgements

We are very grateful to the University of Dundee and the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) for providing the antibody against p-NKCC2.

Funding

This work was supported, in part, by the Technology Star Cultivation Program of the Science and Technology Association of Chongqing (Grant number: KJXX2017017), the Surface project of the Chongqing Municipal Health Bureau (Grant number: 2016MSXM023), the General Program of the National Natural Science Foundation of China (Grant number: 32071110), and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University.

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  1. These authors contributed equally: Yinchuan Lai, Hao Zhou

Authors and Affiliations

  1. Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Cardiac Arrhythmia Therapeutic Service Center, Chongqing Key Laboratory of Arrhythmia, Chongqing, China

    Yinchuan Lai, Hao Zhou, Weijie Chen, Hang Liu, Guangliang Liu, Yanping Xu, Huaan Du, Bo Zhang, Yidan Li & Yuehui Yin

  2. Department of Cardiology, the Second People’s Hospital of Yibin & West China Hospital, Sichuan University Yibin Hospital, Yibin City, Sichuan, China

    Yinchuan Lai

  3. Institute of Future Cities, the Chinese University of Hong Kong, Hong Kong, China

    Kamsang Woo

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Lai, Y., Zhou, H., Chen, W. et al. The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses. Hypertens Res 46, 456–467 (2023). https://doi.org/10.1038/s41440-022-01047-3

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