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Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.
Hypertens Res. 2006 Nov; 29(11):865-74.HR

Abstract

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.

Authors+Show Affiliations

Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. agatajun@yahoo.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17345786

Citation

Agata, Jun, et al. "Olmesartan Is an Angiotensin II Receptor Blocker With an Inhibitory Effect On Angiotensin-converting Enzyme." Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 29, no. 11, 2006, pp. 865-74.
Agata J, Ura N, Yoshida H, et al. Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. Hypertens Res. 2006;29(11):865-74.
Agata, J., Ura, N., Yoshida, H., Shinshi, Y., Sasaki, H., Hyakkoku, M., Taniguchi, S., & Shimamoto, K. (2006). Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 29(11), 865-74.
Agata J, et al. Olmesartan Is an Angiotensin II Receptor Blocker With an Inhibitory Effect On Angiotensin-converting Enzyme. Hypertens Res. 2006;29(11):865-74. PubMed PMID: 17345786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. AU - Agata,Jun, AU - Ura,Nobuyuki, AU - Yoshida,Hideaki, AU - Shinshi,Yasuyuki, AU - Sasaki,Haruki, AU - Hyakkoku,Masaya, AU - Taniguchi,Shinya, AU - Shimamoto,Kazuaki, PY - 2007/3/10/pubmed PY - 2007/4/14/medline PY - 2007/3/10/entrez SP - 865 EP - 74 JF - Hypertension research : official journal of the Japanese Society of Hypertension JO - Hypertens Res VL - 29 IS - 11 N2 - 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. SN - 0916-9636 UR - https://www.unboundmedicine.com/medline/citation/17345786/Olmesartan_is_an_angiotensin_II_receptor_blocker_with_an_inhibitory_effect_on_angiotensin_converting_enzyme_ L2 - https://ClinicalTrials.gov/search/term=17345786 [PUBMED-IDS] DB - PRIME DP - Unbound Medicine ER -