Journal Article

High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage

Stella Bernardi, Barbara Toffoli, Cristina Zennaro, Christos Tikellis, Silvia Monticone, Pasquale Losurdo, Giuseppe Bellini, Merlin C. Thomas, Francesco Fallo, Franco Veglio, Colin I. Johnston and Bruno Fabris

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 5, pages 1793-1800
Published in print May 2012 | ISSN: 0931-0509
Published online October 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr600
High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage

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Background.

Angiotensin II (AngII) contributes to salt-driven kidney damage. In this study, we aimed at investigating whether and how the renal damage associated with a high-salt diet could result from changes in the ratio between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2).

Methods.

Forty-eight rats randomly allocated to three different dietary contents of salt were studied for 4 weeks after undergoing a left uninephrectomy. We focussed on kidney functional, structural and molecular changes. At the same time, we studied kidney molecular changes in 20 weeks old Ace2-knockout mice (Ace2KO), with and without ACE inhibition.

Results.

A high salt content diet significantly increased the glomerular ACE/ACE2 ratio. This was associated with increased oxidative stress. To assess whether these events were related, we measured renal oxidative stress in Ace2KO, and found that the absence of ACE2 promoted oxidative stress, which could be prevented by ACE inhibition.

Conclusion.

One of the mechanisms by which a high-salt diet leads to renal damage seems to be the modulation of the ACE/ACE2 ratio which in turn is critical for the cause of oxidative stress, through AngII.

Keywords: ACE2; glomerulosclerosis; high-salt diet; oxidative stress; sodium

Journal Article.  4836 words.  Illustrated.

Subjects: Nephrology

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