title: The role of apelin on the alleviative effect of Angiotensin receptor blocker in unilateral ureteral obstruction-induced renal fibrosis.
abstract: BACKGROUND
  Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear.
  
  
  METHODS
  We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model.
  
  
  RESULTS
  WE OBTAINED THE FOLLOWING RESULTS: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group.
  
  
  CONCLUSIONS
  These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis.
authors.affiliation: Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nishida
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Okumura
authors.forename: Tatsujiro
authors.initials: T
authors.lastname: Oka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toiyama
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Itoi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamaoka