PMID- 17345786
OWN - NLM
STAT- MEDLINE
DCOM- 20070412
LR  - 20220309
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 29
IP  - 11
DP  - 2006 Nov
TI  - Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on 
      angiotensin-converting enzyme.
PG  - 865-74
AB  - Angiotensin II receptor blockers (ARBs) are widely used for the treatment of 
      hypertension. It is believed that treatment with an ARB increases the level of 
      plasma angiotensin II (Ang II) because of a lack of negative feedback on renin 
      activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that 
      long-term treatment of hypertensive patients with olmesartan resulted in a 
      reduction in plasma Ang II level, though the mechanism was not determined. It has 
      been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of 
      bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is 
      known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 
      2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently 
      been reported that olmesartan increases plasma Ang-(1-7) through an increase in 
      ACE2 expression in rats with myocardial infarction. We hypothesized that 
      over-expression of ACE2 may be related to a reduction in Ang II level and the 
      cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of 
      olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive 
      rats (SHRSP) significantly reduced blood pressure and left ventricular weight 
      compared to those in SHRSP given a vehicle. Co-administration of olmesartan and 
      (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the 
      effect of olmesartan on blood pressure and left ventricular weight. 
      Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan 
      significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to 
      olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly 
      increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats 
      and SHRSP treated with a vehicle. Olmesartan significantly improved 
      cardiovascular remodeling and cardiac nitrite/ nitrate content, but 
      co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this 
      anti-remodeling effect and the increase in nitrite/nitrate. These findings 
      suggest that olmesartan may exhibit an ACE inhibitory action in addition to an 
      Ang II receptor blocking action, prevent an increase in Ang II level, and protect 
      cardiovascular remodeling through an increase in cardiac nitric oxide production 
      and endogenous Ang-(1-7) via over-expression of ACE2.
FAU - Agata, Jun
AU  - Agata J
AD  - Second Department of Internal Medicine, Sapporo Medical University School of 
      Medicine, Sapporo, Japan. agatajun@yahoo.co.jp
FAU - Ura, Nobuyuki
AU  - Ura N
FAU - Yoshida, Hideaki
AU  - Yoshida H
FAU - Shinshi, Yasuyuki
AU  - Shinshi Y
FAU - Sasaki, Haruki
AU  - Sasaki H
FAU - Hyakkoku, Masaya
AU  - Hyakkoku M
FAU - Taniguchi, Shinya
AU  - Taniguchi S
FAU - Shimamoto, Kazuaki
AU  - Shimamoto K
LA  - eng
PT  - Journal Article
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 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Peptide Fragments)
RN  - 0 (Tetrazoles)
RN  - 11128-99-7 (Angiotensin II)
RN  - 4964P6T9RB (Aldosterone)
RN  - 8W1IQP3U10 (olmesartan)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.17.23 (Ace2 protein, rat)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
RN  - EC 3.4.23.15 (Renin)
RN  - IJ3FUK8MOF (angiotensin I (1-7))
SB  - IM
CIN - Hypertens Res. 2006 Nov;29(11):837-8. PMID: 17345782
MH  - Aldosterone/blood
MH  - Angiotensin I
MH  - Angiotensin II/*drug effects
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Angiotensin-Converting Enzyme 2
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Gene Expression
MH  - Imidazoles/*pharmacology
MH  - Male
MH  - Myocardium/metabolism
MH  - Nitrates/metabolism
MH  - Nitrites/metabolism
MH  - Peptide Fragments/*drug effects
MH  - Peptidyl-Dipeptidase A/*drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Renin/blood
MH  - Tetrazoles/*pharmacology
MH  - Ventricular Remodeling/drug effects
EDAT- 2007/03/10 09:00
MHDA- 2007/04/14 09:00
CRDT- 2007/03/10 09:00
PHST- 2007/03/10 09:00 [pubmed]
PHST- 2007/04/14 09:00 [medline]
PHST- 2007/03/10 09:00 [entrez]
AID - 10.1291/hypres.29.865 [doi]
PST - ppublish
SO  - Hypertens Res. 2006 Nov;29(11):865-74. doi: 10.1291/hypres.29.865.