PMID- 19662023
OWN - NLM
STAT- MEDLINE
DCOM- 20091230
LR  - 20200508
IS  - 1348-4214 (Electronic)
IS  - 0916-9636 (Linking)
VI  - 32
IP  - 10
DP  - 2009 Oct
TI  - Significance of angiotensin II receptor blockers with high affinity to 
      angiotensin II type 1 receptors for vascular protection in rats.
PG  - 853-60
LID - 10.1038/hr.2009.116 [doi]
AB  - Angiotensin II receptor blockers (ARBs) vary in their binding affinities to 
      angiotensin II type 1 (AT(1)) receptors in in vitro experiments. We compared a 
      high-affinity ARB, olmesartan, and a low-affinity ARB, valsartan, in terms of 
      their vascular protective effects in stroke-prone spontaneously hypertensive rats 
      (SHR-SP). Blood pressure was equally reduced by placebo, olmesartan (1 mg kg(-1)) 
      and valsartan (3 mg kg(-1)) daily for 2 weeks. In another experiment, 12-week-old 
      SHR-SP were fed 8% salt, and olmesartan (1 mg kg(-1)), valsartan (3 mg kg(-1)) or 
      placebo were administered daily until a survival rate of 60% was reached. In the 
      experiment using SHR-SP, the reduction of acetylcholine-induced vascular 
      relaxation and the increase of p22(phox) expression in the placebo-treated group 
      were significantly attenuated by olmesartan and valsartan, but this attenuation 
      was significantly greater for olmesartan. In immunohistological analysis, all 
      areas positive for angiotensin II, p22(phox) and 4-hydroxy-2-nonenal were 
      significantly reduced by olmesartan and valsartan, but again this reduction was 
      significantly greater for olmesartan. In salt-loaded SHR-SP, the number of days 
      to reach a 60% survival rate was 25 and 42 in placebo and valsartan-treated rats, 
      respectively, and this represented a significant difference. The survival rate in 
      olmesartan-treated rats was 95% at day 42, when valsartan-treated rats reached 
      60% survival, and this difference was also significant. In the surviving rats, 
      olmesartan, but not valsartan, augmented acetylcholine-induced vascular 
      relaxation and attenuated vascular p22(phox) expression. Thus, heterogeneity in 
      binding affinity to AT(1) receptors among ARBs may result in different degrees of 
      vascular protection and lifespan extension.
FAU - Takai, Shinji
AU  - Takai S
AD  - Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki 
      City, Osaka, Japan. pha010@art.osaka-med.ac.jp
FAU - Jin, Denan
AU  - Jin D
FAU - Ikeda, Hironobu
AU  - Ikeda H
FAU - Sakonjo, Hiroshi
AU  - Sakonjo H
FAU - Miyazaki, Mizuo
AU  - Miyazaki M
LA  - eng
PT  - Journal Article
DEP - 20090807
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Imidazoles)
RN  - 0 (Protective Agents)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Sodium-Hydrogen Exchanger 3)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 0 (Tetrazoles)
RN  - 11128-99-7 (Angiotensin II)
RN  - 80M03YXJ7I (Valsartan)
RN  - 8W1IQP3U10 (olmesartan)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (Cyba protein, rat)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.23.15 (Renin)
RN  - HG18B9YRS7 (Valine)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Angiotensin II/metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/*metabolism/*therapeutic use
MH  - Animals
MH  - Carotid Arteries/drug effects
MH  - Hypertension/drug therapy/pathology
MH  - Imidazoles/metabolism/pharmacology
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Male
MH  - Muscle Relaxation/drug effects
MH  - NADPH Oxidases/genetics/metabolism
MH  - Peptidyl-Dipeptidase A/metabolism
MH  - *Protective Agents
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Renin/blood
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sodium-Hydrogen Exchanger 3
MH  - Sodium-Hydrogen Exchangers/metabolism
MH  - Tetrazoles/metabolism/pharmacology
MH  - Valine/analogs & derivatives/metabolism/pharmacology
MH  - Valsartan
MH  - Vascular Diseases/*prevention & control
EDAT- 2009/08/08 09:00
MHDA- 2009/12/31 06:00
CRDT- 2009/08/08 09:00
PHST- 2009/08/08 09:00 [entrez]
PHST- 2009/08/08 09:00 [pubmed]
PHST- 2009/12/31 06:00 [medline]
AID - hr2009116 [pii]
AID - 10.1038/hr.2009.116 [doi]
PST - ppublish
SO  - Hypertens Res. 2009 Oct;32(10):853-60. doi: 10.1038/hr.2009.116. Epub 2009 Aug 7.