title: Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.
abstract: BACKGROUND
  The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging.
  
  
  METHODS
  Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats.
  
  
  RESULTS
  Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats.
  
  
  CONCLUSIONS
  Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly.
authors.forename: Ivonne Hernandez
authors.initials: IH
authors.lastname: Schulman
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Zhou
authors.forename: Adriana V
authors.initials: AV
authors.lastname: Treuer
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Chadipiralla
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Raij
mesh_terms: D000375:Aging / Q000502:physiology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004198:Disease Susceptibility; D005355:Fibrosis; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D011945:Receptors, Angiotensin; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin