PMID- 20353766
OWN - NLM
STAT- MEDLINE
DCOM- 20100809
LR  - 20220310
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 636
IP  - 1-3
DP  - 2010 Jun 25
TI  - Angiotensin II type 1 receptor blockers prevent tumor necrosis 
      factor-alpha-mediated endothelial nitric oxide synthase reduction and superoxide 
      production in human umbilical vein endothelial cells.
PG  - 36-41
LID - 10.1016/j.ejphar.2010.03.025 [doi]
AB  - Decrease in endothelial nitric oxide synthase (eNOS) expression is one of the 
      adverse outcomes of endothelial dysfunction. Tumor necrosis factor-alpha 
      (TNF-alpha) is known to decrease eNOS expression and is an important mediator of 
      endothelial dysfunction. We hypothesized that an angiotensin II type 1 (AT1) 
      receptor blocker would improve endothelial function via not only inhibition of 
      the angiotensin II signaling but also inhibition of the TNF-alpha-mediated 
      signaling. Therefore we investigated whether an AT1 receptor blocker would 
      restore the TNF-alpha-induced decrease in eNOS expression in cultured human 
      umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with an 
      antioxidant (superoxide dismutase, alpha-tocopherol) or AT1 receptor blockers 
      (olmesartan or candesartan) restored the TNF-alpha-dependent reduction of eNOS. 
      The AT1 receptor blocker decreased the TNF-alpha-dependent increase of 
      8-isoprostane. The superoxide dismutase activities in HUVEC were stable during 
      AT1 receptor blocker treatment, and the AT1 receptor blocker did not scavenge 
      superoxide directly. The AT1 receptor blocker also decreased TNF-alpha-induced 
      phosphorylation of I kappaB alpha and cell death. These results suggest that AT1 
      receptor blockers are able to ameliorate TNF-alpha-dependent eNOS reduction or 
      cell injury by inhibiting superoxide production or nuclear factor-kappaB 
      activation.
CI  - (c) 2010 Elsevier B.V. All rights reserved.
FAU - Kataoka, Hiroki
AU  - Kataoka H
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, 65 
      Tsurumai, Showa-ku, Nagoya 466-8550, Japan.
FAU - Murakami, Ryuichiro
AU  - Murakami R
FAU - Numaguchi, Yasushi
AU  - Numaguchi Y
FAU - Okumura, Kenji
AU  - Okumura K
FAU - Murohara, Toyoaki
AU  - Murohara T
LA  - eng
PT  - Journal Article
DEP - 20100329
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Endothelial Cells/cytology/*drug effects/enzymology/*metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Phosphorylation/drug effects
MH  - Superoxides/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Umbilical Veins/*cytology
EDAT- 2010/04/01 06:00
MHDA- 2010/08/10 06:00
CRDT- 2010/04/01 06:00
PHST- 2009/09/01 00:00 [received]
PHST- 2010/01/13 00:00 [revised]
PHST- 2010/03/17 00:00 [accepted]
PHST- 2010/04/01 06:00 [entrez]
PHST- 2010/04/01 06:00 [pubmed]
PHST- 2010/08/10 06:00 [medline]
AID - S0014-2999(10)00221-9 [pii]
AID - 10.1016/j.ejphar.2010.03.025 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 Jun 25;636(1-3):36-41. doi: 10.1016/j.ejphar.2010.03.025. 
      Epub 2010 Mar 29.