Inflammatory Bowel Diseases

Skip Navigation LinksHome > July 2009 - Volume 15 - Issue 7 > Effects of the endothelin‐converting enzyme inhibitor SM‐197...
Inflammatory Bowel Diseases:
doi: 10.1002/ibd.20877
Original Article: Original Basic Science Articles

Effects of the endothelin‐converting enzyme inhibitor SM‐19712 in a mouse model of dextran sodium sulfate‐induced colitis

Lee, Seungjun PhD1; Carter, Patsy R. BS1; Watts, Megan N. BS1; Bao, Jianxiong R. MD, PhD2; Harris, Norman R. PhD1,*

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Background:: Ingestion by mice of dextran sodium sulfate (DSS) induces colonic vasoconstriction and inflammation, with some of the effects potentially mediated by the vasoconstrictor endothelin‐1 (ET‐1).

Methods:: In this study, mice given 5% 40 kD DSS for 5–6 days had elevated colonic immunostaining for ET‐1 and platelet endothelial cell adhesion molecule‐1 (PECAM‐1). Increased ET‐1 can induce microvascular constriction; however, the increase in PECAM‐1 is consistent with angiogenesis that could decrease flow resistance.

Results:: Our measurements of intestinal blood flow, via infused microspheres, suggests that these 2 factors may offset each other, with only a nonsignificant tendency for a DSS‐induced decrease in flow. Daily administration of the endothelin converting enzyme inhibitor SM‐19712 (15 mg/kg) attenuated DSS‐induced increases in colonic immunostaining of ET‐1 and PECAM‐1.

Conclusions:: SM‐19712 attenuated histologic signs of tissue injury and inflammation induced by DSS, and decreased the extent of loose stools and fecal blood. However, the inhibitor did not significantly decrease DSS‐induced colon shortening or tissue levels of myeloperoxidase (an indicator of neutrophil infiltration).

© Crohn's & Colitis Foundation of America, Inc.

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