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Role of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis in the hypotensive effect of azilsartan.
Hypertens Res. 2014 Jul; 37(7):616-20.HR

Abstract

The possible counteracting effect of angiotensin (Ang)-converting enzyme (ACE)2/Ang-(1-7)/Mas axis against the ACE/Ang II/Ang II type 1 (AT1) receptor axis in blood pressure control has been previously described. We examined the possibility that this pathway might be involved in the anti-hypertensive effect of a newly developed AT1 receptor blocker (ARB), azilsartan, and compared azilsartan's effects with those of another ARB, olmesartan. Transgenic mice carrying the human renin and angiotensinogen genes (hRN/hANG-Tg) were given azilsartan or olmesartan. Systolic and diastolic blood pressure, as determined by radiotelemetry, were significantly higher in hRN/hANG-Tg mice than in wild-type (WT) mice. Treatment with azilsartan or olmesartan (1 or 5 mg kg(-1) per day) significantly decreased systolic and diastolic blood pressure, and the blood pressure-lowering effect of azilsartan was more marked than that of olmesartan. The urinary Na concentration decreased in an age-dependent manner in hRN/hANG-Tg mice. Administration of azilsartan or olmesartan increased urinary Na concentration, and this effect was weaker with olmesartan than with azilsartan. Azilsartan decreased ENaC-α mRNA expression in the kidney and decreased the ratio of heart to body weight. Olmesartan had a similar but less-marked effect. ACE2 mRNA expression was lower in the kidneys and hearts of hRN/hANG-Tg mice than in WT mice. This decrease in ACE2 mRNA expression was attenuated by azilsartan, but not by olmesartan. These results suggest that the hypotensive and anti-hypertrophic effects of azilsartan may involve activation of the ACE2/Ang-(1-7)/Mas axis with AT1 receptor blockade.

Authors+Show Affiliations

Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.1] Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan [2] Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.1] Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan [2] Department of Pediatrics, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24599018

Citation

Iwanami, Jun, et al. "Role of Angiotensin-converting Enzyme 2/angiotensin-(1-7)/Mas Axis in the Hypotensive Effect of Azilsartan." Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 37, no. 7, 2014, pp. 616-20.
Iwanami J, Mogi M, Tsukuda K, et al. Role of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis in the hypotensive effect of azilsartan. Hypertens Res. 2014;37(7):616-20.
Iwanami, J., Mogi, M., Tsukuda, K., Wang, X. L., Nakaoka, H., Ohshima, K., Chisaka, T., Bai, H. Y., Kanno, H., Min, L. J., & Horiuchi, M. (2014). Role of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis in the hypotensive effect of azilsartan. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 37(7), 616-20. https://doi.org/10.1038/hr.2014.49
Iwanami J, et al. Role of Angiotensin-converting Enzyme 2/angiotensin-(1-7)/Mas Axis in the Hypotensive Effect of Azilsartan. Hypertens Res. 2014;37(7):616-20. PubMed PMID: 24599018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis in the hypotensive effect of azilsartan. AU - Iwanami,Jun, AU - Mogi,Masaki, AU - Tsukuda,Kana, AU - Wang,Xiao-Li, AU - Nakaoka,Hirotomo, AU - Ohshima,Kousei, AU - Chisaka,Toshiyuki, AU - Bai,Hui-Yu, AU - Kanno,Harumi, AU - Min,Li-Juan, AU - Horiuchi,Masatsugu, Y1 - 2014/03/06/ PY - 2013/10/16/received PY - 2013/11/10/revised PY - 2013/11/14/accepted PY - 2014/3/7/entrez PY - 2014/3/7/pubmed PY - 2015/4/10/medline SP - 616 EP - 20 JF - Hypertension research : official journal of the Japanese Society of Hypertension JO - Hypertens Res VL - 37 IS - 7 N2 - The possible counteracting effect of angiotensin (Ang)-converting enzyme (ACE)2/Ang-(1-7)/Mas axis against the ACE/Ang II/Ang II type 1 (AT1) receptor axis in blood pressure control has been previously described. We examined the possibility that this pathway might be involved in the anti-hypertensive effect of a newly developed AT1 receptor blocker (ARB), azilsartan, and compared azilsartan's effects with those of another ARB, olmesartan. Transgenic mice carrying the human renin and angiotensinogen genes (hRN/hANG-Tg) were given azilsartan or olmesartan. Systolic and diastolic blood pressure, as determined by radiotelemetry, were significantly higher in hRN/hANG-Tg mice than in wild-type (WT) mice. Treatment with azilsartan or olmesartan (1 or 5 mg kg(-1) per day) significantly decreased systolic and diastolic blood pressure, and the blood pressure-lowering effect of azilsartan was more marked than that of olmesartan. The urinary Na concentration decreased in an age-dependent manner in hRN/hANG-Tg mice. Administration of azilsartan or olmesartan increased urinary Na concentration, and this effect was weaker with olmesartan than with azilsartan. Azilsartan decreased ENaC-α mRNA expression in the kidney and decreased the ratio of heart to body weight. Olmesartan had a similar but less-marked effect. ACE2 mRNA expression was lower in the kidneys and hearts of hRN/hANG-Tg mice than in WT mice. This decrease in ACE2 mRNA expression was attenuated by azilsartan, but not by olmesartan. These results suggest that the hypotensive and anti-hypertrophic effects of azilsartan may involve activation of the ACE2/Ang-(1-7)/Mas axis with AT1 receptor blockade. SN - 1348-4214 UR - https://www.unboundmedicine.com/medline/citation/24599018/Role_of_angiotensin_converting_enzyme_2/angiotensin__1_7_/Mas_axis_in_the_hypotensive_effect_of_azilsartan_ L2 - https://medlineplus.gov/bloodpressuremedicines.html DB - PRIME DP - Unbound Medicine ER -