PMID- 25759242
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20151119
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 284
IP  - 3
DP  - 2015 May 1
TI  - Inhibition of NF-kappaB activity in the hypothalamic paraventricular nucleus 
      attenuates hypertension and cardiac hypertrophy by modulating cytokines and 
      attenuating oxidative stress.
PG  - 315-22
LID - S0041-008X(15)00080-0 [pii]
LID - 10.1016/j.taap.2015.02.023 [doi]
AB  - We hypothesized that chronic inhibition of NF-kappaB activity in the hypothalamic 
      paraventricular nucleus (PVN) delays the progression of hypertension and 
      attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, 
      reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-kappaB (NF-kappaB) 
      p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats 
      (SHR). Young normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN 
      infusions with NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 
      4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as 
      indicated by increased whole heart weight/body weight ratio, whole heart 
      weight/tibia length ratio, left ventricular weight/tibia length ratio, 
      cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of 
      cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (beta-MHC). 
      These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), 
      reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 
      (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower 
      PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN 
      infusion of NF-kappaB inhibitor PDTC attenuated all these changes. These findings 
      suggest that NF-kappaB activation in the PVN increases sympathoexcitation and 
      hypertensive response, which are associated with the increases of PICs and 
      oxidative stress in the PVN; PVN inhibition of NF-kappaB activity attenuates PICs and 
      oxidative stress in the PVN, thereby attenuates hypertension and cardiac 
      hypertrophy.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Yu, Xiao-Jing
AU  - Yu XJ
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, 
      Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
FAU - Zhang, Dong-Mei
AU  - Zhang DM
AD  - Department of Physiology, Dalian Medical University, Dalian 116044, China.
FAU - Jia, Lin-Lin
AU  - Jia LL
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, 
      Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
FAU - Qi, Jie
AU  - Qi J
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, 
      Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
FAU - Song, Xin-Ai
AU  - Song XA
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, 
      Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
FAU - Tan, Hong
AU  - Tan H
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, 
      Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
FAU - Cui, Wei
AU  - Cui W
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an 
      710061, China.
FAU - Chen, Wensheng
AU  - Chen W
AD  - Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an 710032, China.
FAU - Zhu, Guo-Qing
AU  - Zhu GQ
AD  - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department 
      of Physiology, Nanjing Medical University, Nanjing 210029, China.
FAU - Qin, Da-Nian
AU  - Qin DN
AD  - Department of Physiology, Shantou University Medical College, Shantou 515041, 
      China. Electronic address: dnqin@stu.edu.cn.
FAU - Kang, Yu-Ming
AU  - Kang YM
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, 
      Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. Electronic 
      address: ykang@mail.xjtu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150307
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Pyrrolidines)
RN  - 0 (Rela protein, rat)
RN  - 0 (Thiocarbamates)
RN  - 0 (Transcription Factor RelA)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
SB  - IM
MH  - Animals
MH  - Arterial Pressure/drug effects
MH  - Biomarkers/metabolism
MH  - Cardiomegaly/etiology/immunology/metabolism/physiopathology/*prevention & control
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Hypertension/complications/*drug therapy/immunology/metabolism/physiopathology
MH  - Inflammation Mediators/*metabolism
MH  - Oxidative Stress/*drug effects
MH  - Paraventricular Hypothalamic Nucleus/*drug effects/immunology/metabolism
MH  - Pyrrolidines/*pharmacology
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Signal Transduction/drug effects
MH  - Sympathetic Nervous System/drug effects/metabolism/physiopathology
MH  - Thiocarbamates/*pharmacology
MH  - Time Factors
MH  - Transcription Factor RelA/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Cardiac hypertrophy
OT  - Hypertension
OT  - Hypothalamic paraventricular nucleus
OT  - NF-kappaB
OT  - Neurohormonal excitation
EDAT- 2015/03/12 06:00
MHDA- 2015/06/30 06:00
CRDT- 2015/03/12 06:00
PHST- 2014/11/18 00:00 [received]
PHST- 2015/02/18 00:00 [revised]
PHST- 2015/02/25 00:00 [accepted]
PHST- 2015/03/12 06:00 [entrez]
PHST- 2015/03/12 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
AID - S0041-008X(15)00080-0 [pii]
AID - 10.1016/j.taap.2015.02.023 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2015 May 1;284(3):315-22. doi: 
      10.1016/j.taap.2015.02.023. Epub 2015 Mar 7.