PMID- 20718738
OWN - NLM
STAT- MEDLINE
DCOM- 20101228
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 161
IP  - 1
DP  - 2010 Sep
TI  - Angiotensin receptor type 1 antagonists protect against neuronal injury induced 
      by oxygen-glucose depletion.
PG  - 33-50
LID - 10.1111/j.1476-5381.2010.00840.x [doi]
AB  - BACKGROUND AND PURPOSE: Several clinical trials and in vivo animal experiments 
      have suggested that blockade of angiotensin receptor type 1 (AT(1)) improves 
      ischaemic outcomes. However, the mechanism(s) underlying these effects has not 
      been elucidated. Here, we have investigated the protective effects of 
      pretreatment with AT(1) receptor antagonists, losartan or telmisartan, against 
      ischaemic insult to neurons in vitro. EXPERIMENTAL APPROACH: Primary rat 
      neuron-astrocyte co-cultures and astrocyte-defined medium (ADM)-cultured pure 
      astrocyte cultures were prepared. Ischaemic injury was modelled by oxygen-glucose 
      depletion (OGD) and lactate dehydrogenase release after OGD was measured with or 
      without AT(1) receptor antagonists or agonists (L162313), AT(2) receptor 
      antagonist (PD123319) or agonist (CGP-42112A) pretreatment, for 48 h. Activity of 
      glutamate transporter 1 (GLT-1) was evaluated by [(3)H]-glutamate uptake assays, 
      after AT(1) receptor agonists or antagonists. Immunoblot and real-time PCR were 
      used for analysis of protein and mRNA levels of GLT-1. KEY RESULTS: AT(1) 
      receptor agonists augmented OGD-induced cellular damage, which was attenuated by 
      AT(1) receptor antagonists. AT(1) receptor antagonists also suppressed 
      OGD-induced extracellular glutamate release, reactive oxygen species production 
      and nitric oxide generation. GLT-1 expression and glutamate uptake activity were 
      significantly enhanced by AT(1) receptor antagonists and impaired by AT(1) 
      receptor agonists. AT(1) receptor stimulation suppressed both ADM-induced GLT-1 
      protein expression and mRNA levels. AT(1)b receptor knock-down with siRNA 
      enhanced GLT-1 expression. In postnatal (P1-P21) rat brains, protein levels of 
      GLT-1 and AT(1) receptors were inversely correlated. CONCLUSIONS AND 
      IMPLICATIONS: Suppression of AT(1) receptor stimulation induced GLT-1 
      up-regulation, which ameliorated effects of ischaemic injury.
FAU - Wu, X
AU  - Wu X
AD  - Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical 
      Sciences, Kyoto University, Kyoto, Japan.
FAU - Kihara, T
AU  - Kihara T
FAU - Hongo, H
AU  - Hongo H
FAU - Akaike, A
AU  - Akaike A
FAU - Niidome, T
AU  - Niidome T
FAU - Sugimoto, H
AU  - Sugimoto H
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoates)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Imidazoles)
RN  - 0 (L 162313)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - IY9XDZ35W2 (Glucose)
RN  - JMS50MPO89 (Losartan)
RN  - S88TT14065 (Oxygen)
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Animals
MH  - Astrocytes
MH  - Benzimidazoles/*pharmacology
MH  - Benzoates/*pharmacology
MH  - Biphenyl Compounds/pharmacology
MH  - Cell Death
MH  - Coculture Techniques
MH  - Excitatory Amino Acid Transporter 2/genetics/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/*metabolism
MH  - Glutamic Acid/metabolism
MH  - Imidazoles/pharmacology
MH  - Losartan/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Nitric Oxide/metabolism
MH  - Oxygen/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Telmisartan
PMC - PMC2962815
EDAT- 2010/08/20 06:00
MHDA- 2010/12/29 06:00
PMCR- 2011/09/01
CRDT- 2010/08/20 06:00
PHST- 2010/08/20 06:00 [entrez]
PHST- 2010/08/20 06:00 [pubmed]
PHST- 2010/12/29 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - BPH840 [pii]
AID - 10.1111/j.1476-5381.2010.00840.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2010 Sep;161(1):33-50. doi: 10.1111/j.1476-5381.2010.00840.x.