title: Activation of intrarenal renin-angiotensin system during metabolic acidosis.
abstract: 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.
  
  
  CONCLUSIONS
  Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Hwee-Yeong
authors.initials: HY
authors.lastname: Ng
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chen
authors.forename: Yu-Che
authors.initials: YC
authors.lastname: Tsai
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Yang
authors.forename: Chien-Te
authors.initials: CT
authors.lastname: Lee
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000643:Ammonium Chloride; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D016212:Transforming Growth Factor beta; D000643:Ammonium Chloride; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A