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


CONCLUSIONS
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.
Department of Morphology and Embriology, University of Ferrara, Ferrara, Italy. stella.bernardi@bakeridi.edu.au
Stella
S
Bernardi
Barbara
B
Toffoli
Cristina
C
Zennaro
Christos
C
Tikellis
Silvia
S
Monticone
Pasquale
P
Losurdo
Giuseppe
G
Bellini
Merlin C
MC
Thomas
Francesco
F
Fallo
Franco
F
Veglio
Colin I
CI
Johnston
Bruno
B
Fabris
D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004195:Disease Models, Animal; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*
D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2