Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats

Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxy...

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Autores principales:	Qing Su, Xiao-Jing Yu, Xiao-Min Wang, Hong-Bao Li, Ying Li, Juan Bai, Jie Qi, Nianping Zhang, Kai-Li Liu, Yan Zhang, Guo-Qing Zhu, Yu-Ming Kang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	salt-induced hypertension Ec-SOD NLRP3 neurotransmitters paraventricular nucleus Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/23bbe02bb51a4a1cbde2759576756c07
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spelling	oai:doaj.org-article:23bbe02bb51a4a1cbde2759576756c072021-12-01T01:33:53ZBilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats1663-981210.3389/fphar.2021.756671https://doaj.org/article/23bbe02bb51a4a1cbde2759576756c072021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.756671/fullhttps://doaj.org/toc/1663-9812Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear.Methods: Sprague–Dawley rats (150–200 g) were fed either a high salt diet (8% NaCl, HS) or normal salt diet (0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks.Results: High salt intake not only increased mean arterial blood pressure (MAP) and the plasma noradrenaline (NE) but also elevated the NAD(P)H oxidase activity, the NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the NOD-like receptor protein 3 (NLRP3)–dependent inflammatory proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the tyrosine hydroxylase (TH) expression in the PVN with high salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and GABA level in the PVN compared with the high salt group.Conclusion: Excessive salt intake not only activates oxidative stress but also induces the NLRP3-depensent inflammation and breaks the balance between inhibitory and excitability neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent inflammation and improving the excitatory neurotransmitter release in the PVN in the salt-induced hypertension.Qing SuXiao-Jing YuXiao-Min WangHong-Bao LiYing LiJuan BaiJie QiNianping ZhangKai-Li LiuYan ZhangGuo-Qing ZhuYu-Ming KangFrontiers Media S.A.articlesalt-induced hypertensionEc-SODNLRP3neurotransmittersparaventricular nucleusTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	salt-induced hypertension Ec-SOD NLRP3 neurotransmitters paraventricular nucleus Therapeutics. Pharmacology RM1-950
spellingShingle	salt-induced hypertension Ec-SOD NLRP3 neurotransmitters paraventricular nucleus Therapeutics. Pharmacology RM1-950 Qing Su Xiao-Jing Yu Xiao-Min Wang Hong-Bao Li Ying Li Juan Bai Jie Qi Nianping Zhang Kai-Li Liu Yan Zhang Guo-Qing Zhu Yu-Ming Kang Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats
description	Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear.Methods: Sprague–Dawley rats (150–200 g) were fed either a high salt diet (8% NaCl, HS) or normal salt diet (0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks.Results: High salt intake not only increased mean arterial blood pressure (MAP) and the plasma noradrenaline (NE) but also elevated the NAD(P)H oxidase activity, the NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the NOD-like receptor protein 3 (NLRP3)–dependent inflammatory proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the tyrosine hydroxylase (TH) expression in the PVN with high salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and GABA level in the PVN compared with the high salt group.Conclusion: Excessive salt intake not only activates oxidative stress but also induces the NLRP3-depensent inflammation and breaks the balance between inhibitory and excitability neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent inflammation and improving the excitatory neurotransmitter release in the PVN in the salt-induced hypertension.
format	article
author	Qing Su Xiao-Jing Yu Xiao-Min Wang Hong-Bao Li Ying Li Juan Bai Jie Qi Nianping Zhang Kai-Li Liu Yan Zhang Guo-Qing Zhu Yu-Ming Kang
author_facet	Qing Su Xiao-Jing Yu Xiao-Min Wang Hong-Bao Li Ying Li Juan Bai Jie Qi Nianping Zhang Kai-Li Liu Yan Zhang Guo-Qing Zhu Yu-Ming Kang
author_sort	Qing Su
title	Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats
title_short	Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats
title_full	Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats
title_fullStr	Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats
title_full_unstemmed	Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats
title_sort	bilateral paraventricular nucleus upregulation of extracellular superoxide dismutase decreases blood pressure by regulation of the nlrp3 and neurotransmitters in salt-induced hypertensive rats
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/23bbe02bb51a4a1cbde2759576756c07
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Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats

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