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Effects of renal denervation at BP-elevation/reduction sites guided by renal nerve stimulation on atrial neural and structural remodeling in a hypertensive canine model

Hypertension Research volume 48, pages 2387–2400 (2025)Cite this article

Abstract

Hypertension is a common condition in cardiovascular medicine, and can lead to atrial enlargement, atrial fibrosis, and even the development of atrial fibrillation. Renal denervation (RDN) causes reduction in blood pressure (BP), but its effects on hypertension-related atrial remodeling remain unclear. This study aimed to explore the effects of RDN at BP-elevation/reduction sites guided by renal nerve stimulation (RNS) on atrial neural and structural remodeling in a hypertensive canine model. The twenty-four Chinese Kunming dogs were divided into three groups: (1) the reduced BP response ablation group (RRA group, n = 8), (2) the renal stimulation control group (RSC group, n = 8), and (3) the elevated BP response ablation group (ERA group, n = 8), which were followed for 4 weeks. Our results showed that in terms of atrial neural remodeling, compared with the RSC group, the ERA group exhibited reduced tyrosine hydroxylase (TH) protein expression and a lower TH/ choline acetyltransferase (ChAT) ratio. In contrast, the RRA group showed lower ChAT and muscarinic acetylcholine receptor 2 (CM2) protein expression, and an elevated TH/ChAT ratio. Compared with the RSC group, the ERA group presented a smaller myocyte area, reduced collagen I protein expression, and lower myocardial interstitial collagen fiber content. In contrast, the RRA group presented a larger myocyte area, increased collagen I protein expression, and greater collagen fiber content. Overall, RDN at elevated BP response sites improved atrial neural and structural remodeling under hypertensive conditions, whereas RDN at reduced BP response sites exacerbated the imbalance between atrial sympathetic and parasympathetic nerve activity and worsened structural remodeling.

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Acknowledgements

We would like to express our gratitude to American Journal Experts for their invaluable assistance in the language editing of this manuscript. This study was supported by the National Natural Science Foundation of China (Grant Numbers: 32071110 and Yin Yue-Hui) and the Natural Science Foundation of Chongqing, China (No. CSTB2024NSCQ-MSX0595 Chen Wei-Jie).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Cardiovascular Neuromodulation Research and Treatment Center, Chongqing Key Lab of Arrhythmia, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Dan Li, Yuxiang Long, Hao Zhou, Weijie Chen, Yinchuan Lai, Yiwen Ren, Xiaomin Ma, Hongyu Kuang, Xinyu Hu, Guangliang Liu, Zhiyu Ling, Peilin Xiao & Yuehui Yin

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  1. Dan Li
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Contributions

DL contributed to conceptualization, methodology, software development, formal analysis, investigation, data curation, original draft preparation, and review and editing. YL, HZ, WC, YL, YR, and XM contributed to the methodology, formal analysis, investigation, data curation, visualization, review and editing. HK, XH, GL, and ZL contributed resources, data curation, review and editing, and visualization. PX and YY contributed to conceptualization, methodology, validation, review and editing, supervision, and project administration. All the authors gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.

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Correspondence to Peilin Xiao or Yuehui Yin.

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This study was approved by the Animal Experiment Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University, following the guidelines of the National Institutes of Health for the care and use of laboratory animals, and standard experimental animal care was provided at the Animal Experiment Center of Chongqing Medical University.

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Dan Li, Long, Y., Zhou, H. et al. Effects of renal denervation at BP-elevation/reduction sites guided by renal nerve stimulation on atrial neural and structural remodeling in a hypertensive canine model. Hypertens Res 48, 2387–2400 (2025). https://doi.org/10.1038/s41440-025-02258-0

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