title: Angiotensin-Converting Enzyme Inhibitor (ACEI)-Mediated Amelioration in Renal Fibrosis Involves Suppression of Mast Cell Degranulation.
abstract: OBJECTIVE
  The mechanism by which angiotensin-converting enzyme inhibitors (ACEIs) attenuate renal fibrosis has not been fully uncovered.
  
  
  METHODS
  Renal fibrosis in rats was triggered by unilateral ureteral obstruction (UUO) and treated with Enalapril.
  
  
  RESULTS
  Enalapril attenuated renal fibrosis, as evidenced by the fibrosis scores (1.07±0.73 versus 2.18±0.75 for 200 mg/ml Enalapril versus control, p<0.01) of Enalapril-treated UUO rats compared to mock-treated UUO rats. The amelioration was mast cell dependent, as Enalapril exhibited no effects on mast cell-deficient Kit(wsh/wsh) mice developing renal fibrosis. We detected lower levels of transforming growth factor β (TGF-β) and alpha-smooth muscle actin (α-SMA, a fibroblast activation marker) in the kidney tissue of Enalapril-treated UUO rats relative to the control UUO rats. Enalapril-treated UUO rats exhibited far fewer mast cells infiltrating per area in the kidney tissue than the control UUO rats (8.00±0.65 versus 29.00±0.57, p<0.01). Electron microscopy images revealed that mast cell degranulation was inhibited by Enalapril treatment. Further, IgE-mediated passive cutaneous anaphylaxis demonstrated that Enalapril blocked mast cell degranulation in vivo.
  
  
  CONCLUSIONS
  Enalapril attenuated renal fibrosis in UUO rats, possibly by a mechanism involving the suppression of mast cell degranulation.
authors.affiliation: Department of Nephropathy, The Affiliated Hospital of Logistics University of the People's Armed Police Force, Tianjin, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Shi
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D005355:Fibrosis; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology*; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors