PMID- 25131447
OWN - NLM
STAT- MEDLINE
DCOM- 20150602
LR  - 20140929
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 71
DP  - 2014 Nov
TI  - Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 
      as a novel mechanism for pressor response after ischemic stroke.
PG  - 292-304
LID - S0969-9961(14)00234-4 [pii]
LID - 10.1016/j.nbd.2014.08.005 [doi]
AB  - Pressor response after stroke commonly leads to early death or susceptibility to 
      stroke recurrence, and detailed mechanisms are still lacking. We assessed the 
      hypothesis that the renin-angiotensin system contributes to pressor response 
      after stroke by differential modulation of the pro-inflammatory chemokine 
      monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla 
      (RVLM), a key brain stem site that maintains blood pressure. We also investigated 
      the beneficial effects of a novel renin inhibitor, aliskiren, against 
      stroke-elicited pressor response. Experiments were performed in male adult 
      Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited 
      significant pressor response, accompanied by activation of angiotensin II (Ang 
      II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and 
      Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 
      (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor 
      response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 
      signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. 
      Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R 
      activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren 
      inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity 
      and reduced neuroinflammation in the RVLM; these effects were potentiated by 
      Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R 
      signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes 
      pressor response after stroke by differential modulations of MCP-1 in the RVLM. 
      Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into 
      the brain stem provides more effective amelioration of stroked-induced pressor 
      response.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Chang, Alice Y W
AU  - Chang AY
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan, ROC; Department of Physiology, National 
      Cheng Kung University, Tainan, Taiwan, ROC; Department of Pharmacology, Kaohsiung 
      Medical University, Kaohsiung, Taiwan, ROC; Department of Biological Science, 
      National Sun Yat-sen University, Kaohsiung, Taiwan, ROC. Electronic address: 
      aywchang@mail.ncku.edu.tw.
FAU - Li, Faith C H
AU  - Li FC
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan, ROC.
FAU - Huang, Chi-Wei
AU  - Huang CW
AD  - Department of Biological Science, National Sun Yat-sen University, Kaohsiung, 
      Taiwan, ROC; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, 
      Kaohsiung, Taiwan, ROC.
FAU - Wu, Julie C C
AU  - Wu JC
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan, ROC.
FAU - Dai, Kuang-Yu
AU  - Dai KY
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan, ROC.
FAU - Chen, Chang-Han
AU  - Chen CH
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan, ROC.
FAU - Li, Shau-Hsuan
AU  - Li SH
AD  - Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital, 
      Kaohsiung, Taiwan, ROC.
FAU - Su, Chia-Hao
AU  - Su CH
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital, Kaohsiung, Taiwan, ROC.
FAU - Wu, Re-Wen
AU  - Wu RW
AD  - Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan, ROC.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140812
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Angiotensins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Analysis of Variance
MH  - Angiotensins/genetics/*metabolism
MH  - Animals
MH  - Blood Pressure/*physiology
MH  - Brain Ischemia/complications
MH  - Brain Stem/*metabolism
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*physiology
MH  - Heart Rate/physiology
MH  - Male
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neurologic Examination
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke/etiology/metabolism/*pathology
OTO - NOTNLM
OT  - Aliskiren
OT  - Angiotensin isoforms and receptors
OT  - Ischemic stroke
OT  - Middle cerebral artery occlusion
OT  - Monocyte chemoattractant protein-1
OT  - Neuroinflammation
OT  - Pressor response after stroke
OT  - Rostral ventrolateral medulla
EDAT- 2014/08/19 06:00
MHDA- 2015/06/03 06:00
CRDT- 2014/08/19 06:00
PHST- 2014/01/04 00:00 [received]
PHST- 2014/07/03 00:00 [revised]
PHST- 2014/08/02 00:00 [accepted]
PHST- 2014/08/19 06:00 [entrez]
PHST- 2014/08/19 06:00 [pubmed]
PHST- 2015/06/03 06:00 [medline]
AID - S0969-9961(14)00234-4 [pii]
AID - 10.1016/j.nbd.2014.08.005 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2014 Nov;71:292-304. doi: 10.1016/j.nbd.2014.08.005. Epub 2014 Aug 
      12.