title: Aliskiren ameliorates renal inflammation and fibrosis induced by unilateral ureteral obstruction in mice.
abstract: OBJECTIVE
  Renin-angiotensin system activation is involved in inflammation and fibrosis in the kidney. Aliskiren, a direct renin inhibitor, decreases renin-angiotensin system activation, including plasma renin activity and angiotensin II, but increases the prorenin level, which may promote inflammation and fibrosis in renal tissue. Thus, we evaluated whether inhibiting the renin-angiotensin system by aliskiren would decrease renal inflammation and fibrosis in a mouse model of unilateral ureteral obstruction.
  
  
  METHODS
  Ten-week-old male C57BL/6 mice (Samtako, Kyoung Gi-Do, Korea) weighing 30 to 33 gm were divided into 4 groups, including vehicle or aliskiren treated sham operated and vehicle or aliskiren treated unilateral ureteral obstruction groups. We evaluated plasma renin activity, and plasma renin and renal mRNA expression levels of renin and (pro)renin receptor. To evaluate inflammation and fibrosis renal mRNA expression of monocyte chemotactic protein-1, osteopontin and transforming growth factor-β was measured. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemical staining for CD68, transforming growth factor-β and α-smooth muscle actin were performed.
  
  
  RESULTS
  Plasma renin activity was significantly lower in the aliskiren treated obstruction group than in the vehicle treated obstruction group. Aliskiren treatment increased renal mRNA expression of renin. The number of CD68 positive cells, and renal monocyte chemotactic protein-1 and osteopontin mRNA levels were significantly higher in mice with unilateral ureteral obstruction than in sham operated mice. Aliskiren decreased the increased levels of these inflammation markers. Aliskiren also decreased renal transforming growth factor-β mRNA expression, transforming growth factor-β and α-smooth muscle actin immunostaining, and Masson's trichrome stained areas of unilateral ureteral obstruction kidneys.
  
  
  CONCLUSIONS
  Aliskiren has anti-inflammatory and antifibrotic effects in an experimental unilateral ureteral obstruction mouse model.
authors.affiliation: Department of Nephrology, Chungnam National University Hospital, Daejeon, South Korea.
authors.forename: Dae Eun
authors.initials: DE
authors.lastname: Choi
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Jeong
authors.forename: Beom Jin
authors.initials: BJ
authors.lastname: Lim
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Chang
authors.forename: Ki-Ryang
authors.initials: KR
authors.lastname: Na
authors.forename: Young-Tai
authors.initials: YT
authors.lastname: Shin
authors.forename: Kang Wook
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology; D005650:Fumarates / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000188:drug therapy* / Q000209:etiology; D014517:Ureteral Obstruction / Q000150:complications; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren