title: Protective effects of angiotensin-(1-7) administrated with an angiotensin-receptor blocker in a rat model of chronic kidney disease.
abstract: OBJECTIVE
  Angiotensin-(1-7) (Ang-(1-7)) opposes angiotensin-II-induced cell growth, matrix accumulation and fibrosis in cardiac tissue. However, the role of Ang-(1-7) in the pathogenesis of renal fibrosis is uncertain. This study observed the effects of Ang-(1-7), on its own or in combination with losartan, an angiotensin-receptor blocker, on five-sixths nephrectomized rats.
  
  
  METHODS
  Male Sprague-Dawley rats underwent five-sixths nephrectomy, and then were either untreated, treated with Ang-(1-7), treated with losartan, or treated with a combination therapy of Ang-(1-7) and losartan. After 8 weeks, renal function was assessed by measuring systolic blood pressure, serum creatinine and proteinuria. The effect of nephrectomy on the renin-angiotensin system was examined by measuring plasma levels of Ang-II and Ang-(1-7). The extent of glomerulosclerosis and tubulointerstitial fibrosis was assessed by periodic acid-Schiff staining and Masson-trichrome staining. The expression of plasminogen activator inhibitor-1, fibronectin and angiopoietins-Tie-2 was investigated by immunohistochemistry and western blot.
  
  
  RESULTS
  In the groups of treated rats, serum creatinine, proteinuria and markers of glomerulosclerosis, such as fibronectin and plasminogen activator inhibitor-1, were ameliorated compared with the untreated, nephrectomized rats. Plasma Ang-(1-7) levels were elevated in all treatment groups, but the plasma Ang-II levels were reduced in the Ang-(1-7)-treated group and the combination therapy group. The ratio of Ang-1/Ang-2 was increased in the combination therapy group compared with two other treatment groups.
  
  
  CONCLUSIONS
  Ang-(1-7) ameliorated the renal injury of nephrectomized rats. The combination of Ang-(1-7) treatment alongside losartan exerted a superior effect to that of Ang-(1-7) alone on regression of glomerulosclerosis.
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Shanghai, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D042682:Angiopoietins / Q000032:analysis; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005353:Fibronectins / Q000032:analysis; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009392:Nephrectomy; D010446:Peptide Fragments / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000032:analysis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D013599:Systole
chemical_list: D042682:Angiopoietins; D047228:Angiotensin II Type 1 Receptor Blockers; D005353:Fibronectins; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D000804:Angiotensin II; D000803:Angiotensin I; D042787:Receptor, TIE-2; C118790:angiotensin I (1-7); D019808:Losartan
keywords: angiogenesis; angiotensin; chronic kidney disease