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Role of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis in the hypotensive effect of azilsartan.
Iwanami, Jun; Mogi, Masaki; Tsukuda, Kana; Wang, Xiao-Li; Nakaoka, Hirotomo; Ohshima, Kousei; Chisaka, Toshiyuki; Bai, Hui-Yu; Kanno, Harumi; Min, Li-Juan; Horiuchi, Masatsugu.
Afiliación
  • Iwanami J; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Mogi M; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Tsukuda K; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Wang XL; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Nakaoka H; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Ohshima K; 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.
  • Chisaka T; 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.
  • Bai HY; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Kanno H; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Min LJ; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
  • Horiuchi M; Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Ehime, Japan.
Hypertens Res ; 37(7): 616-20, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24599018
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxadiazoles / Fragmentos de Péptidos / Bencimidazoles / Angiotensina I / Proteínas Proto-Oncogénicas / Peptidil-Dipeptidasa A / Receptores Acoplados a Proteínas G / Bloqueadores del Receptor Tipo 1 de Angiotensina II / Antihipertensivos Límite: Animals Idioma: En Revista: Hypertens Res Asunto de la revista: ANGIOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxadiazoles / Fragmentos de Péptidos / Bencimidazoles / Angiotensina I / Proteínas Proto-Oncogénicas / Peptidil-Dipeptidasa A / Receptores Acoplados a Proteínas G / Bloqueadores del Receptor Tipo 1 de Angiotensina II / Antihipertensivos Límite: Animals Idioma: En Revista: Hypertens Res Asunto de la revista: ANGIOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido