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Short hairpin RNA interference targeting interleukin 1 receptor type I in the paraventricular nucleus attenuates hypertension in rats

  • Signalling and cell physiology
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Abstract

Blood pressure is controlled by tonic sympathetic activities, excessive activation of which contributes to the pathogenesis and progression of hypertension. Interleukin (IL)-1β in the paraventricular nucleus (PVN) is involved in sympathetic overdrive and hypertension. Here, we investigated the therapeutic effects of IL-1 receptor type I (IL-1R1) gene silencing in the PVN on hypertension. Recombinant lentivirus vectors expressing a short hairpin RNA (shRNA) targeting IL-1R1 (Lv-shR-IL-1R1) or a control shRNA were microinjected into PVN of spontaneously hypertensive rats (SHRs) and normotensive WKY rats. The fluorescence of green fluorescent protein-labelled vectors appeared at 2 weeks after injection and persisted for at least 8 weeks. IL-1R1 protein expression in the PVN was reduced 4 weeks after Lv-shR-IL-1R1 injection in SHRs. IL-1R1 interference also reduced basal sympathetic activity, cardiac sympathetic afferent reflex in SHRs. Depressor effects were observed from week 2 to 10 after Lv-shR-IL-1R1 treatment in SHRs, with the most prominent effects seen at the end of week 4. Furthermore, Lv-shR-IL-1R1 treatment decreased the ratio of left ventricular weight to body weight and cross-sectional areas of myocardial cells in SHRs. Additionally, Lv-shR-IL-1R1 treatment prevented an increase in superoxide anion and pro-inflammatory cytokines (PICs, TNF-α and IL-1β) in the PVN of SHR, and upregulated anti-inflammatory cytokine (AIC, IL-10) expression. These results indicate that shRNA interference targeting IL-1R1 in the PVN decreases arterial blood pressure, attenuates excessive sympathetic activity and cardiac sympathetic afferent reflex, and improves myocardial remodelling in SHRs by restoring the balance between PICs and AICs to attenuate oxidative stress.

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Acknowledgements

The authors would like to thank Professor Guo-qing Zhu, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, for his technical assistance. They are also grateful to Zhi-dan Fan, Lei Zhang, and Peng Li for their help with experiments.

Funding

This project was supported by funding under the International Cooperation Program for Excellent Lectures of 2015 by Shandong Provincial Education Department, P.R. China, grants from the National Natural Science Foundation of China (81200186), Shandong Provincial Natural Science Foundation, China (BS2015YY036), and Shandong Provincial Medical and Health Science and Technology Development Plan (2016WS0051). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Education, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264003, China

    Peng Lu

  2. Department of Physiology, Binzhou Medical University, 346 Guanhai Rd, Laishan District, Yantai, Shandong Province, 264003, China

    Shu-jun Jiang, Hong Pan, Ai-li Xu, Chun-lei Ma & Zhen Shi

  3. Experimental Teaching Management Center, Binzhou Medical University, Yantai, 264003, China

    Gui-hua Wang

  4. Shandong Province Key Laboratory of Stroke, Yantai, 264003, China

    Peng Lu & Chun-lei Ma

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  1. Peng Lu
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Correspondence to Zhen Shi.

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All animal work in this study was approved and performed in accordance with the Home Office UK Animals (Scientific Procedures) Act 1986 under the regulations and policies laid out by the Medical Ethics Committee of Binzhou Medical University.

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Lu, P., Jiang, Sj., Pan, H. et al. Short hairpin RNA interference targeting interleukin 1 receptor type I in the paraventricular nucleus attenuates hypertension in rats. Pflugers Arch - Eur J Physiol 470, 439–448 (2018). https://doi.org/10.1007/s00424-017-2081-0

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