Dextran sulfate sodium-induced acute colonic inflammation in angiotensin II type 1a receptor deficient mice.

Abstract

OBJECTIVE:

Angiotensin II (Ang II) receptor blockers have been reported to contribute to cytoprotective effects in various organs. However, the role of renin-angiotensin system (RAS) in modulation of the inflammatory bowel disease (IBD) remains unclear. In this study we assessed the role of angiotensin II type 1a (AT1a) receptor on the outcome of dextran sulfate sodium (DSS)-induced acute colitis by employing AT1a receptor deficient mice.

MATERIALS AND METHODS:

The acute colitis was induced in wild type (WT) and AT1a receptor deficient mice by giving orally 3% DSS in drinking water for 7 days.

RESULTS:

Induction of DSS colitis resulted in up-regulation of Ang II and AT1a receptor in the colonic mucosa of WT mice. In parallel, loss of body weight, an increase in disease activity index (DAI), and the shortening of colon were found in DSS-challenged WT mice. In addition, an increase in thiobarbituric acid (TBA)-reactive substances and myeloperoxidase (MPO) activity, along with the up-regulation of tumor necrosis factor (TNF)-alpha were detected in the colonic mucosa of DSS-challenged WT mice. The endpoints mentioned above were significantly ameliorated in DSS-challenged AT1a receptor deficient mice.

CONCLUSIONS:

RAS is involved in the pathophysiology of DSS-induced colitis and AT1a receptor may be a novel therapeutic target for the treatment of IBD.

• Authors: K Katada, N Yoshida, T Suzuki, T Okuda, K Mizushima, T Takagi, H Ichikawa, Y Naito, G Cepinskas, T Yoshikawa
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 57 Issue 2 Pg. 84-91 (Feb 2008) ISSN: 1023-3830 [Print] Switzerland
• PMID: 18288458 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, Angiotensin, Type 1
• Tumor Necrosis Factor-alpha
• Angiotensin II
• Dextran Sulfate
• Peroxidase

Topics

• Angiotensin II (metabolism)
• Animals
• Body Weight
• Colitis (chemically induced)
• Colon (pathology)
• Dextran Sulfate (pharmacology)
• Inflammation
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Peroxidase (metabolism)
• Receptor, Angiotensin, Type 1 (genetics, physiology)
• Renin-Angiotensin System
• Tumor Necrosis Factor-alpha (metabolism)