PMID- 23877628
OWN - NLM
STAT- MEDLINE
DCOM- 20140811
LR  - 20131122
IS  - 1559-0259 (Electronic)
IS  - 1530-7905 (Linking)
VI  - 13
IP  - 4
DP  - 2013 Dec
TI  - Interaction between AT1 receptor and NF-kappaB in hypothalamic paraventricular 
      nucleus contributes to oxidative stress and sympathoexcitation by modulating 
      neurotransmitters in heart failure.
PG  - 381-90
LID - 10.1007/s12012-013-9219-x [doi]
AB  - Angiotensin II type 1 receptor (AT1-R) and nuclear factor-kappaB (NF-kappaB) in the 
      paraventricular nucleus (PVN) play important roles in heart failure (HF); 
      however, the central mechanisms by which AT1-R and NF-kappaB contribute to 
      sympathoexcitation in HF are yet unclear. In this study, we determined whether 
      interaction between AT1-R and NF-kappaB in the PVN modulates neurotransmitters and 
      contributes to NAD(P)H oxidase-dependent oxidative stress and sympathoexcitation 
      in HF. Rats were implanted with bilateral PVN cannulae and subjected to coronary 
      artery ligation or sham surgery (SHAM). Subsequently, animals were treated for 4 
      weeks through bilateral PVN infusion with either vehicle or losartan (LOS, 
      10 mug/h), an AT1-R antagonist; or pyrrolidine dithiocarbamate (PDTC, 5 mug/h), a 
      NF-kappaB inhibitor via osmotic minipump. Myocardial infarction (MI) rats had higher 
      levels of glutamate (Glu), norepinephrine (NE) and NF-kappaB p65 activity, lower 
      levels of gamma-aminobutyric acid (GABA), and more positive neurons for 
      phosphorylated IKKbeta and gp91(phox) (a subunit of NAD(P)H oxidase) in the PVN when 
      compared to SHAM rats. MI rats also had higher levels of renal sympathetic nerve 
      activity (RSNA) and plasma proinflammatory cytokines (PICs), NE and epinephrine. 
      PVN infusions of LOS or PDTC attenuated the decreases in GABA and the increases 
      in gp91(phox), NF-kappaB activity, Glu and NE, in the PVN of HF rats. PVN infusions 
      of LOS or PDTC also attenuated the increases in RSNA and plasma PICs, NE and 
      epinephrine in MI rats. These findings suggest that interaction between AT1 
      receptor and NF-kappaB in the PVN contributes to oxidative stress and 
      sympathoexcitation by modulating neurotransmitters in heart failure.
FAU - Yu, Xiao-Jing
AU  - Yu XJ
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, 
      Xi'an, 710061, China.
FAU - Suo, Yu-Ping
AU  - Suo YP
FAU - Qi, Jie
AU  - Qi J
FAU - Yang, Qing
AU  - Yang Q
FAU - Li, Hui-Hua
AU  - Li HH
FAU - Zhang, Dong-Mei
AU  - Zhang DM
FAU - Yi, Qiu-Yue
AU  - Yi QY
FAU - Zhang, Jian
AU  - Zhang J
FAU - Zhu, Guo-Qing
AU  - Zhu GQ
FAU - Zhu, Zhiming
AU  - Zhu Z
FAU - Kang, Yu-Ming
AU  - Kang YM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cardiovasc Toxicol
JT  - Cardiovascular toxicology
JID - 101135818
RN  - 0 (NF-kappa B)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Thiocarbamates)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Animals
MH  - Heart Failure/*metabolism
MH  - Losartan/pharmacology
MH  - Male
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Neurotransmitter Agents/physiology
MH  - Oxidative Stress/drug effects/*physiology
MH  - Paraventricular Hypothalamic Nucleus/drug effects/*metabolism
MH  - Protein Binding/physiology
MH  - Pyrrolidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Sympathetic Fibers, Postganglionic/drug effects/*metabolism
MH  - Thiocarbamates/pharmacology
EDAT- 2013/07/24 06:00
MHDA- 2014/08/12 06:00
CRDT- 2013/07/24 06:00
PHST- 2013/07/24 06:00 [entrez]
PHST- 2013/07/24 06:00 [pubmed]
PHST- 2014/08/12 06:00 [medline]
AID - 10.1007/s12012-013-9219-x [doi]
PST - ppublish
SO  - Cardiovasc Toxicol. 2013 Dec;13(4):381-90. doi: 10.1007/s12012-013-9219-x.