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Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats.
Toxicol Appl Pharmacol 2017; 333:100-109TA

Abstract

Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important transcription factor that modulates cell antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of tert-butylhydroquinone (tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. These rats were chronic bilateral PVN infusion of tBHQ (0.8μg/day), or oxygen free radical scavenger tempol (20μg/h), or vehicle for 2weeks. SHR rats had higher mean arterial pressure (MAP), plasma norepinephrine (NE) levels, and sympathetic nerve activity (RSNA) and lower PVN levels of Nrf2, hemeoxygenase-1 (HO-1), superoxide dismutase-1 (SOD1) and catalase (CAT) as compared with those in the WKY group. Bilateral PVN infusion of tBHQ or tempol significantly reduced MAP, RSNA, plasma NE levels in SHR rats. In addition, tBHQ treatment enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1, CAT and SOD1 in SHR rats. Furthermore, tBHQ attenuated PVN levels of ROS, the expression of proinflammatory cytokines and restored the imbalance of neurotransmitters in PVN. Knockdown of Nrf2 in the PVN by adeno-associated virus mediated small interfering RNA abrogated the protective effects of tBHQ on hypertension. These findings suggest that PVN administration of tBHQ can attenuate hypertension by activation of the Nrf2-mediated signaling pathway.

Authors+Show Affiliations

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China. Electronic address: yuxiaojing@mail.xjtu.edu.cn.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China. Electronic address: ykang@mail.xjtu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28842207

Citation

Bai, Juan, et al. "Central Administration of Tert-butylhydroquinone Attenuates Hypertension Via Regulating Nrf2 Signaling in the Hypothalamic Paraventricular Nucleus of Hypertensive Rats." Toxicology and Applied Pharmacology, vol. 333, 2017, pp. 100-109.
Bai J, Yu XJ, Liu KL, et al. Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats. Toxicol Appl Pharmacol. 2017;333:100-109.
Bai, J., Yu, X. J., Liu, K. L., Wang, F. F., Jing, G. X., Li, H. B., ... Kang, Y. M. (2017). Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats. Toxicology and Applied Pharmacology, 333, pp. 100-109. doi:10.1016/j.taap.2017.08.012.
Bai J, et al. Central Administration of Tert-butylhydroquinone Attenuates Hypertension Via Regulating Nrf2 Signaling in the Hypothalamic Paraventricular Nucleus of Hypertensive Rats. Toxicol Appl Pharmacol. 2017 10 15;333:100-109. PubMed PMID: 28842207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats. AU - Bai,Juan, AU - Yu,Xiao-Jing, AU - Liu,Kai-Li, AU - Wang,Fang-Fang, AU - Jing,Gui-Xia, AU - Li,Hong-Bao, AU - Zhang,Yan, AU - Huo,Chan-Juan, AU - Li,Xiang, AU - Gao,Hong-Li, AU - Qi,Jie, AU - Kang,Yu-Ming, Y1 - 2017/08/24/ PY - 2017/05/13/received PY - 2017/08/15/revised PY - 2017/08/21/accepted PY - 2017/8/27/pubmed PY - 2017/9/21/medline PY - 2017/8/27/entrez KW - Hypertension KW - Nrf2 KW - Oxidative stress KW - Paraventricular nucleus KW - Tert-butylhydroquinone SP - 100 EP - 109 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 333 N2 - Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important transcription factor that modulates cell antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of tert-butylhydroquinone (tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. These rats were chronic bilateral PVN infusion of tBHQ (0.8μg/day), or oxygen free radical scavenger tempol (20μg/h), or vehicle for 2weeks. SHR rats had higher mean arterial pressure (MAP), plasma norepinephrine (NE) levels, and sympathetic nerve activity (RSNA) and lower PVN levels of Nrf2, hemeoxygenase-1 (HO-1), superoxide dismutase-1 (SOD1) and catalase (CAT) as compared with those in the WKY group. Bilateral PVN infusion of tBHQ or tempol significantly reduced MAP, RSNA, plasma NE levels in SHR rats. In addition, tBHQ treatment enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1, CAT and SOD1 in SHR rats. Furthermore, tBHQ attenuated PVN levels of ROS, the expression of proinflammatory cytokines and restored the imbalance of neurotransmitters in PVN. Knockdown of Nrf2 in the PVN by adeno-associated virus mediated small interfering RNA abrogated the protective effects of tBHQ on hypertension. These findings suggest that PVN administration of tBHQ can attenuate hypertension by activation of the Nrf2-mediated signaling pathway. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/28842207/Central_administration_of_tert_butylhydroquinone_attenuates_hypertension_via_regulating_Nrf2_signaling_in_the_hypothalamic_paraventricular_nucleus_of_hypertensive_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(17)30349-6 DB - PRIME DP - Unbound Medicine ER -