Activation of intrarenal renin-angiotensin system during metabolic acidosis

Am J Nephrol. 2011;34(1):55-63. doi: 10.1159/000328742. Epub 2011 Jun 10.


Background: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear.

Methods: Male Sprague-Dawley rats were fed with water containing 0.14 M NH(4)Cl to induce metabolic acidosis for 1 and 8 weeks, respectively. They were compared with animals fed with deionized water (control) and equimolar sodium chloride water (NaCl). Gene expression analysis of RAS components included renin, renin/prorenin receptor, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 and 2 receptors (AT1R and AT2R). Histological examination was also performed to detect morphological change.

Results: Acidosis was found in 1-week NH(4)Cl-treated rats but not in the 8-week group. More than twofold proteinuria and a significant decline of glomerular filtration rate (GFR) were observed in acid-loaded rats. Compared to the control and NaCl groups, angiotensinogen, ACE, AT1R and AT2R were significantly increased in the 1-week acidosis group (all p < 0.05). Sustained increase of AT1R expression was found as NH(4)Cl was continued for 8 weeks. There was no significant change in transforming growth factor-β and nuclear factor-κB. The architecture of tubular epithelial cells was affected during our experiment.

Conclusion: Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / chemically induced
  • Acidosis / metabolism*
  • Acidosis / pathology
  • Ammonium Chloride
  • Angiotensinogen / metabolism
  • Animals
  • Gene Expression
  • Glomerular Filtration Rate
  • Male
  • NF-kappa B / metabolism
  • Peptidyl-Dipeptidase A / metabolism
  • Proteinuria
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / metabolism
  • Renin-Angiotensin System / genetics
  • Renin-Angiotensin System / physiology*
  • Time Factors
  • Transforming Growth Factor beta / metabolism


  • NF-kappa B
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Transforming Growth Factor beta
  • Ammonium Chloride
  • Angiotensinogen
  • Peptidyl-Dipeptidase A