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Superoxide anions mediate the effects of angiotensin (1-7) analog, alamandine, on blood pressure and sympathetic activity in the paraventricular nucleus.

Abstract

Microinjection of alamandine into the hypothalamic paraventricular nucleus (PVN) increased blood pressure and enhanced sympathetic activity. The aim of this study was to determine if superoxide anions modulate alamandine's effects in the PVN. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Microinjection of alamandine into the PVN increased MAP and RSNA in both WKY rats and SHRs, although to a greater extent in SHRs. These effects were blocked by pretreatment with an alamandine receptor (MrgD) antagonist D-Pro7-Ang-(1-7). Pretreatment with superoxide anion scavengers, tempol and tiron, and NADPH oxidase inhibitor apocynin (APO), also blocked the effects of alamandine on MAP and RSNA. In addition, pretreatment in the PVN with a superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) potentiated the increases of MAP and RSNA induced by alamandine administration, with a greater response observed in SHRs. Superoxide anions and NADPH oxidase levels in the PVN were higher in SHRs than that in WKY rats. Alamandine treatment increased the levels of superoxide anions and NADPH oxidase in WKY and SHRs, however, with greater effect in SHRs. These alamandine-induced increases were inhibited by D-Pro7-Ang-(1-7) pretreatment in the PVN of both rats. These results demonstrate that superoxide anions in the PVN modulate alamandine-induced increases in blood pressure and sympathetic activity in both normotensive and hypertensive rats. Alamandine increases NADPH oxidase activity to induce superoxide anion production, which is mediated by the alamandine receptor.

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  • Authors+Show Affiliations

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Cardiology, the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: yhsheng@njmu.edu.cn.

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    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: bin.zhou@einstein.yu.edu.

    Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: xiangqing_kong@sina.com.

    Source

    Peptides 118: 2019 Jun 11 pg 170101

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31199949

    Citation

    Gong, Juexiao, et al. "Superoxide Anions Mediate the Effects of Angiotensin (1-7) Analog, Alamandine, On Blood Pressure and Sympathetic Activity in the Paraventricular Nucleus." Peptides, vol. 118, 2019, p. 170101.
    Gong J, Shen Y, Li P, et al. Superoxide anions mediate the effects of angiotensin (1-7) analog, alamandine, on blood pressure and sympathetic activity in the paraventricular nucleus. Peptides. 2019;118:170101.
    Gong, J., Shen, Y., Li, P., Zhao, K., Chen, X., Li, Y., ... Kong, X. (2019). Superoxide anions mediate the effects of angiotensin (1-7) analog, alamandine, on blood pressure and sympathetic activity in the paraventricular nucleus. Peptides, 118, p. 170101. doi:10.1016/j.peptides.2019.170101.
    Gong J, et al. Superoxide Anions Mediate the Effects of Angiotensin (1-7) Analog, Alamandine, On Blood Pressure and Sympathetic Activity in the Paraventricular Nucleus. Peptides. 2019 Jun 11;118:170101. PubMed PMID: 31199949.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Superoxide anions mediate the effects of angiotensin (1-7) analog, alamandine, on blood pressure and sympathetic activity in the paraventricular nucleus. AU - Gong,Juexiao, AU - Shen,Yihui, AU - Li,Peng, AU - Zhao,Kun, AU - Chen,Xuguan, AU - Li,Yong, AU - Sheng,Yanhui, AU - Zhou,Bin, AU - Kong,Xiangqing, Y1 - 2019/06/11/ PY - 2019/04/12/received PY - 2019/06/07/revised PY - 2019/06/07/accepted PY - 2019/6/15/pubmed PY - 2019/6/15/medline PY - 2019/6/15/entrez KW - Alamandine KW - NADPH oxidase KW - Paraventricular nucleus KW - Spontaneously hypertensive rat KW - Superoxide anion SP - 170101 EP - 170101 JF - Peptides JO - Peptides VL - 118 N2 - Microinjection of alamandine into the hypothalamic paraventricular nucleus (PVN) increased blood pressure and enhanced sympathetic activity. The aim of this study was to determine if superoxide anions modulate alamandine's effects in the PVN. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Microinjection of alamandine into the PVN increased MAP and RSNA in both WKY rats and SHRs, although to a greater extent in SHRs. These effects were blocked by pretreatment with an alamandine receptor (MrgD) antagonist D-Pro7-Ang-(1-7). Pretreatment with superoxide anion scavengers, tempol and tiron, and NADPH oxidase inhibitor apocynin (APO), also blocked the effects of alamandine on MAP and RSNA. In addition, pretreatment in the PVN with a superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) potentiated the increases of MAP and RSNA induced by alamandine administration, with a greater response observed in SHRs. Superoxide anions and NADPH oxidase levels in the PVN were higher in SHRs than that in WKY rats. Alamandine treatment increased the levels of superoxide anions and NADPH oxidase in WKY and SHRs, however, with greater effect in SHRs. These alamandine-induced increases were inhibited by D-Pro7-Ang-(1-7) pretreatment in the PVN of both rats. These results demonstrate that superoxide anions in the PVN modulate alamandine-induced increases in blood pressure and sympathetic activity in both normotensive and hypertensive rats. Alamandine increases NADPH oxidase activity to induce superoxide anion production, which is mediated by the alamandine receptor. SN - 1873-5169 UR - https://www.unboundmedicine.com/medline/citation/31199949/Superoxide_anions_mediate_the_effects_of_angiotensin_(1-7)_analog,_alamandine,_on_blood_pressure_and_sympathetic_activity_in_the_paraventricular_nucleus L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(19)30079-8 DB - PRIME DP - Unbound Medicine ER -