PMID- 23211364
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20211203
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 344
IP  - 2
DP  - 2013 Feb
TI  - AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator.
PG  - 348-59
LID - 10.1124/jpet.112.197483 [doi]
AB  - Candesartan is an angiotensin II type 1 receptor blocker (ARB) that has been to 
      shown to limit ischemic stroke and improve stroke outcome. In experimental 
      stroke, candesartan induces a proangiogenic effect that is partly attributable to 
      vascular endothelial growth factor. Brain-derived neurotrophic factor (BDNF) is a 
      member of the neurotrophin family that has been reported to have angiogenic 
      effects and play an important role in recovery after stroke. The purpose of this 
      investigation was to determine the role of BDNF in the proangiogenic effect of 
      candesartan in the brain under hypertensive conditions. Accordingly, 
      spontaneously hypertensive rats were treated with candesartan, and brain tissue 
      samples were collected for quantification of BDNF expression. In addition, human 
      cerebromicrovascular endothelial cells were treated with either low-dose (1 fM) 
      or high-dose (1 microM) angiotensin II alone or in combination with candesartan (0.16 
      microM) to assess the effect of candesartan treatment and BDNF involvement in the 
      behavior of endothelial cells. Candesartan significantly increased the expression 
      of BDNF in the SHR (P < 0.05). In addition, candesartan reversed the 
      antiangiogenic effect of the 1-microM dose of AngII (P = 0.0001). The observed 
      effects of candesartan were ablated by neutralizing the effects of BDNF. 
      Treatment with the AT2 antagonist PD-123319 significantly reduced tube-like 
      formation in endothelial cells. AT2 stimulation induced the BDNF expression and 
      migration (P < 0.05). In conclusion, candesartan exerts a proangiogenic effect on 
      brain microvascular endothelial cells treated with angiotensin II. This response 
      is attributable to increased BDNF expression and is mediated through stimulation 
      of the AT2 receptor.
FAU - Alhusban, Ahmed
AU  - Alhusban A
AD  - Program in Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, USA.
FAU - Kozak, Anna
AU  - Kozak A
FAU - Ergul, Adviye
AU  - Ergul A
FAU - Fagan, Susan C
AU  - Fagan SC
LA  - eng
GR  - NS070239/NS/NINDS NIH HHS/United States
GR  - R01 NS063965/NS/NINDS NIH HHS/United States
GR  - I01 BX000891/BX/BLRD VA/United States
GR  - NS063965/NS/NINDS NIH HHS/United States
GR  - R01 NS083559/NS/NINDS NIH HHS/United States
GR  - I01 BX000347/BX/BLRD VA/United States
GR  - R21 NS070239/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121204
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Tetrazoles)
RN  - S8Q36MD2XX (candesartan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology/therapeutic use
MH  - Animals
MH  - Benzimidazoles/*pharmacology/therapeutic use
MH  - Biphenyl Compounds
MH  - Blotting, Western
MH  - Brain/blood supply/*drug effects
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - Hypertension/drug therapy/metabolism
MH  - Male
MH  - Neovascularization, Physiologic/*drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Tetrazoles/*pharmacology/therapeutic use
PMC - PMC3558823
EDAT- 2012/12/06 06:00
MHDA- 2013/03/30 06:00
PMCR- 2014/02/01
CRDT- 2012/12/06 06:00
PHST- 2012/12/06 06:00 [entrez]
PHST- 2012/12/06 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - jpet.112.197483 [pii]
AID - JPET_197483 [pii]
AID - 10.1124/jpet.112.197483 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2013 Feb;344(2):348-59. doi: 10.1124/jpet.112.197483. Epub 
      2012 Dec 4.