Skip Navigation


NDT Advance Access originally published online on February 26, 2007
Nephrology Dialysis Transplantation 2007 22(5):1314-1322; doi:10.1093/ndt/gfl780
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/5/1314    most recent
gfl780v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in NDT
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Onozato, M. L.
Right arrow Articles by Fujita, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Onozato, M. L.
Right arrow Articles by Fujita, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Dual blockade of aldosterone and angiotensin II additively suppresses TGF-ß and NADPH oxidase in the hypertensive kidney

Maristela Lika Onozato1, Akihiro Tojo1, Naohiko Kobayashi2, Atsuo Goto1, Hiroaki Matsuoka2 and Toshiro Fujita1

1Division of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan and 2Division of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Tochigi, Japan

Correspondence and offprint requests to: Akihiro Tojo, MD, Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: tojyo-2im{at}h.u-tokyo.ac.jp



  Abstract

Background. Angiotensin II blockade and spironolactone effectively reduces proteinuria in humans. To clarify the mechanisms of the beneficial effect of blockade of both aldosterone and angiotensin II, we associated the aldosterone antagonist eplerenone to an angiotensin-converting enzyme inhibitor (ACEI) and examined the effect on renal transforming growth factor (TGF)-ß expression and oxidative stress by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the Dahl salt-sensitive rat with heart failure (DSHF).

Methods. Dahl salt-resistant control rats and DSHF rats were fed with 8% NaCl diet and at 11 weeks the DSHF rats were treated with vehicle, eplerenone (Epl), trandolapril or a combination of both drugs for 7 weeks.

Results. DSHF rats showed increased NADPH oxidase and decreased superoxide dismutase (SOD) resulting in increased oxidative stress. ACEI and Epl reduced NADPH oxidase showing an additive effect in their combination; ACEI increased manganese SOD (MnSOD) and Epl increased MnSOD, copper–zinc SOD and catalase, resulting in the lowest levels of oxidative stress with the combination therapy. Glomerulosclerosis and proteinuria were increased in the DSHF rats, and Epl suppressed them more effectively than ACEI to levels not different from the combination of both, showing a positive correlation with NADPH oxidase expression and TGF-ß. Renal TGF-ß was specifically suppressed with Epl

Conclusion. The association of Epl to ACEI is beneficial due to further reduction of NADPH oxidase and specific inhibition of TGF-ß resulting in improvement of renal damage.

Keywords: ACE inhibitor; eplerenone; hypertension; NADPH oxidase; oxidative stress, TGF-ß

Received for publication: 30. 7.06
Accepted in revised form: 1.12.06


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?

Related articles in NDT:

In this issue ...

NDT 2007 22: i. [Extract] [FREE Full Text]  



This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
A. Whaley-Connell, J. Habibi, Y. Wei, A. Gutweiler, J. Jellison, C. E. Wiedmeyer, C. M. Ferrario, and J. R. Sowers
Mineralocorticoid receptor antagonism attenuates glomerular filtration barrier remodeling in the transgenic Ren2 rat
Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1013 - F1022.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Z. Zheng, H. Chen, G. Ke, Y. Fan, H. Zou, X. Sun, Q. Gu, X. Xu, and P. C.P. Ho
Protective Effect of Perindopril on Diabetic Retinopathy Is Associated With Decreased Vascular Endothelial Growth Factor-to-Pigment Epithelium-Derived Factor Ratio: Involvement of a Mitochondria-Reactive Oxygen Species Pathway
Diabetes, April 1, 2009; 58(4): 954 - 964.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
Y. S. Kang, G. J. Ko, M. H. Lee, H. K. Song, S. Y. Han, K. H. Han, H. K. Kim, J. Y. Han, and D. R. Cha
Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats
Nephrol. Dial. Transplant., January 1, 2009; 24(1): 73 - 84.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
S. Zhu, Y. Liu, L. Wang, and Q. H. Meng
Transforming growth factor-{beta}1 is associated with kidney damage in patients with essential hypertension: renoprotective effect of ACE inhibitor and/or angiotensin II receptor blocker
Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2841 - 2846.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A.C. Montezano, G.E. Callera, A. Yogi, Y. He, R.C. Tostes, G. He, E.L. Schiffrin, and R.M. Touyz
Aldosterone and Angiotensin II Synergistically Stimulate Migration in Vascular Smooth Muscle Cells Through c-Src-Regulated Redox-Sensitive RhoA Pathways
Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1511 - 1518.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
W. Huang, C. Xu, K. W. Kahng, N. A. Noble, W. A. Border, and Y. Huang
Aldosterone and TGF-{beta}1 synergistically increase PAI-1 and decrease matrix degradation in rat renal mesangial and fibroblast cells
Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1287 - F1295.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. L. Tarry-Adkins, J. A. Joles, J.-H. Chen, M. S. Martin-Gronert, D. M. van der Giezen, R. Goldschmeding, C. N. Hales, and S. E. Ozanne
Protein restriction in lactation confers nephroprotective effects in the male rat and is associated with increased antioxidant expression
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1259 - R1266.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.