title: Atrial natriuretic peptide ameliorates peritoneal fibrosis in rat peritonitis model.
abstract: BACKGROUND
  Atrial natriuretic peptide (ANP) was recently reported to ameliorate fibrosis in the heart and experimental renal diseases and vascular thickening after balloon injury. Peritoneal fibrosis is an important complication of long-term peritoneal dialysis, and peritonitis is a factor in its onset. In the present study, we investigated the effects of ANP in a rat peritonitis-induced peritoneal fibrosis model.
  
  
  METHODS
  As pretreatment, an osmotic pump containing vehicle (saline) or ANP (0.15 or 0.3 μg/min) was inserted through the carotid vein in male Sprague-Dawley rats. ANP or saline was continuously infused using the osmotic pump. Three days after administration of ANP or saline, rats underwent peritoneal scraping in a blind manner and were sacrificed on Day 14. The effects of ANP were evaluated based on peritoneal thickness, immunohistochemistry and real-time polymerase chain reaction. In each experiment, we evaluated messenger RNA (mRNA) expression of the ANP receptor natriuretic peptide receptor A (NPR-A) in the peritoneum after scraping. The effects of ANP were also studied in cultured peritoneal fibroblasts and mesothelial cells.
  
  
  RESULTS
  We observed a significant increase in NPR-A mRNA in the peritoneum. Peritoneal thickness increased with time and peaked on Day 14, but ANP significantly reduced peritoneal thickness. Parameters such as number of macrophages and CD-31-positive vessels and expression of type III collagen/transforming growth factor-β/plasminogen activator inhibitor-1 (PAI-1)/connective tissue growth factor (CTGF) were significantly suppressed by ANP. In cultured peritoneal fibroblasts and mesothelial cells, ANP suppressed angiotensin II-induced upregulation of CTGF and PAI-1.
  
  
  CONCLUSIONS
  Our results suggest that ANP is useful in preventing inflammation-induced peritoneal fibrosis.
authors.affiliation: Department of Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.forename: Akiho
authors.initials: A
authors.lastname: Sawai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kinashi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nagura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D001707:Biopsy, Needle; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D008297:Male; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D010538:Peritonitis / Q000188:drug therapy / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A