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Renin–Angiotensin System Modulates Neurotransmitters in the Paraventricular Nucleus and Contributes to Angiotensin II-Induced Hypertensive Response

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Abstract

Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether renin–angiotensin system (RAS) activation in the hypothalamic paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive response via interaction with neurotransmitters in the PVN. Rats underwent subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS), an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these findings suggest that the RAS activation in the PVN contributes to the ANG II-induced hypertensive response via interaction with PIC and neurotransmitters (glutamate, NE and GABA) in the PVN.

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Acknowledgments

This study was supported by National Basic Research Program of China (No. 2012CB517805), National Natural Science Foundation of China (Nos. 81170248, 81070199), Research Fund for the Doctoral Program of Higher Education of China (No. 20101417110002), Shanxi Natural Science Foundation (No. 2010011052-1) and Fundamental Research Funds for the Central Universities of China (No. 08142001).

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an Jiaotong University School of Medicine, Xi’an, 710061, China

    Jie Qi, Xin-Ai Song, Xiao-Jing Yu, Yuan-Xi Lin & Yu-Ming Kang

  2. Department of Physiology, Shanxi Medical University, Taiyuan, China

    Yan-Yan Xu

  3. Department of Pharmacology, Xi’an Jiaotong University School of Medicine, Xi’an, China

    Wei-Jin Zang

  4. Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Chongqing Institute of Hypertension, The Third Military Medical University, Chongqing, China

    Zhiming Zhu

  5. Department of Physiology, Dalian Medical University, Dalian, China

    Dong-Mei Zhang

  6. Department of Obstetrics and Gynecology, Shanxi Provincial People’s Hospital, Taiyuan, China

    Yu-Ping Suo

  7. Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Carrie Elks

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  1. Jie Qi
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Correspondence to Yu-Ming Kang.

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The authors Jie Qi, Dong-Mei Zhang, Yu-Ping Suo and Xin-Ai Song contributed equally to this study.

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Qi, J., Zhang, DM., Suo, YP. et al. Renin–Angiotensin System Modulates Neurotransmitters in the Paraventricular Nucleus and Contributes to Angiotensin II-Induced Hypertensive Response. Cardiovasc Toxicol 13, 48–54 (2013). https://doi.org/10.1007/s12012-012-9184-9

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  • DOI: https://doi.org/10.1007/s12012-012-9184-9

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