High-salt Diet Increases Glomerular ACE/ACE2 Ratio Leading to Oxidative Stress and Kidney Damage

Nephrol Dial Transplant. 2012 May;27(5):1793-800. doi: 10.1093/ndt/gfr600. Epub 2011 Oct 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Disease Models, Animal
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism*
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephrectomy
  • Oxidative Stress / drug effects*
  • Peptidyl-Dipeptidase A / deficiency
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System / physiology
  • Sodium Chloride, Dietary / adverse effects
  • Sodium Chloride, Dietary / pharmacology*


  • Sodium Chloride, Dietary
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2