Clinical and Experimental Nephrology

, Volume 18, Issue 4, pp 593–599

Renin inhibition ameliorates renal damage through prominent suppression of both angiotensin I and II in human renin angiotensinogen transgenic mice with high salt loading

  • Shigetaka Yoshida
  • Kenichi Ishizawa
  • Nobuhiro Ayuzawa
  • Kohei Ueda
  • Maki Takeuchi
  • Wakako Kawarazaki
  • Toshiro Fujita
  • Miki Nagase
Original Article



The renin–angiotensin–aldosterone system (RAAS) plays pivotal roles in the pathogenesis of chronic kidney disease (CKD) progression. Aliskiren, a direct renin inhibitor, inhibits the rate-limiting step of the RAAS without any alternative pathway. It is proven to reduce albuminuria in CKD patients treated with angiotensin blockade. However, there are few reports which evaluate the advantage of aliskiren as the first-line drug against CKD progression in RAAS-activated hypertensive patients.


Tsukuba hypertensive mice (THM), double transgenic mice carrying both the human renin and human angiotensinogen genes, were fed a high-salt diet and treated with hydraladine, ramipril and aliskiren for 10 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks during the experimental period. We evaluated renal histological changes and gene expression. Plasma angiotensin concentration was measured to evaluate the RAAS inhibitory effect.


High-salt-loaded THM showed severe hypertension and renal injury. All antihypertensive drugs suppressed blood pressure and prevented renal disease progression. RAAS blockade showed a higher renoprotective effect than hydraladine despite an equivalent blood pressure lowering effect. Aliskiren exhibited even stronger renoprotection than ramipril. Plasma angiotensin concentration was increased in THM fed both normal salt and high salt. Hydraladine did not alter the plasma angiotensin concentration. Ramipril significantly decreased angiotensin II concentration. Aliskiren treatment almost completely suppressed angiotensin I and resulted in lower angiotensin II concentration than ramipril treatment.


Aliskiren prevents renal disease progression by suppressing both angiotensin I and II in RAAS-activated pathology. Our data suggest the application of a renin inhibitor for preventing kidney disease progression in CKD patients.


Aliskiren Hypertension RAAS Tsukuba hypertensive mouse Renin Angiotensin 

Supplementary material

10157_2013_893_MOESM1_ESM.doc (326 kb)
Supplementary material 1 (DOC 326 kb)


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Copyright information

© Japanese Society of Nephrology 2013

Authors and Affiliations

  • Shigetaka Yoshida
    • 1
  • Kenichi Ishizawa
    • 1
  • Nobuhiro Ayuzawa
    • 1
  • Kohei Ueda
    • 1
  • Maki Takeuchi
    • 1
  • Wakako Kawarazaki
    • 2
  • Toshiro Fujita
    • 2
  • Miki Nagase
    • 1
  1. 1.Department of Nephrology and EndocrinologyThe University of Tokyo Graduate School of MedicineTokyoJapan
  2. 2.Department of Clinical EpigeneticsThe University of Tokyo Research Center for Advanced Science and TechnologyTokyoJapan

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