Journal Article

Atrial natriuretic peptide ameliorates peritoneal fibrosis in rat peritonitis model

Hiroshi Kato, Tomohiro Mizuno, Masashi Mizuno, Akiho Sawai, Yasuhiro Suzuki, Hiroshi Kinashi, Fumiko Nagura, Shoichi Maruyama, Yukihiro Noda, Kiyofumi Yamada, Seiichi Matsuo and Yasuhiko Ito

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 2, pages 526-536
Published in print February 2012 | ISSN: 0931-0509
Published online June 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr302
Atrial natriuretic peptide ameliorates peritoneal fibrosis in rat peritonitis model

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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.

Keywords: ANP; CTGF; peritoneal fibrosis; renin-angiotensin system; TGF-β

Journal Article.  4706 words.  Illustrated.

Subjects: Nephrology

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