title: Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension.
abstract: OBJECTIVE
  To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin-angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension.
  
  
  RESULTS
  Male Sprague-Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91(phox) (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1 beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91(phox), ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats.
  
  
  CONCLUSIONS
  These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension.
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou 515041, China. Electronic address: dnqin@stu.edu.cn.
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Qin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, China.
authors.forename: Fu-Xin
authors.initials: FX
authors.lastname: Wang
authors.affiliation: Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Hong-Bao
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Yu-Wang
authors.initials: YW
authors.lastname: Miao
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
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, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China. Electronic address: ykang@mail.xjtu.edu.cn.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000032:analysis*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000032:analysis; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D013113:Spin Labels; D000804:Angiotensin II; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A; C001803:tempol
keywords: Hypertension; Hypothalamic paraventricular nucleus; Oxidative stress; Proinflammatory cytokines; Renin–angiotensin system