title: Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines.
abstract: Reactive oxygen species (ROS) in the brain are involved in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. This study was designed to determine whether chronic infusion of EGCG into the hypothalamic paraventricular nucleus (PVN) attenuates ROS and sympathetic activity and delays the progression of hypertension by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and decreasing nuclear factor-kappa B (NF-κB) activity, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) rats and SHR received bilateral PVN infusion of EGCG (20μg/h) or vehicle via osmotic minipumps for 4 weeks. SHR showed higher mean arterial pressure, plasma proinflammatory cytokines and circulating norepinephrine (NE) levels compared with WKY rats. SHR also had higher PVN levels of the subunit of NAD(P)H oxidase (gp91phox), ROS, tyrosine hydroxylase, and PICs; increased NF-κB activity; and lower PVN levels of interleukin-10 (IL-10) and 67kDa isoform of glutamate decarboxylase (GAD67) than WKY rats. PVN infusion of EGCG attenuated all these changes in SHR. These findings suggest that SHR have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN. Chronic inhibition of ROS in the PVN restores the balance of neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive response and sympathetic activity.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China; Department of Cardiovascular Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Yi
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Hong-Bao
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Huo
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Gao
authors.affiliation: Department of Cardiovascular Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Kou
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Shi
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China. Electronic address: ykang@mail.xjtu.edu.cn.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy*; D007267:Injections; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018377:Neurotransmitter Agents; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D009638:Norepinephrine
keywords: Cytokines; Epigallocatechin-3-O-gallate; Hypertension; Neurotransmitters; Oxidative stress; Paraventricular nucleus