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

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

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Abstract

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). 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. 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. 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.

Original languageEnglish
Pages (from-to)1793-1800
Number of pages8
JournalNephrology Dialysis Transplantation
Volume27
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Cite this

Bernardi, S., Toffoli, B., Zennaro, C., Tikellis, C., Monticone, S., Losurdo, P., Bellini, G., Thomas, M. C., Fallo, F., Veglio, F., Johnston, C. I., & Fabris, B. (2012). High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage. Nephrology Dialysis Transplantation, 27(5), 1793-1800. https://doi.org/10.1093/ndt/gfr600