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An endothelin converting enzyme inhibitor (SM‐19712) attenuates dextran sodium sulfate (DSS)‐induced colitis in mice
Author(s) -
Lee Seungjun,
Carter Patsy R.,
Watts Megan N.,
Bao Jianxiong R.,
Harris Norman R.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.762.12
Subject(s) - chemistry , vasoconstriction , endothelin 1 , immunostaining , inflammation , colitis , myeloperoxidase , angiogenesis , endocrinology , endothelin receptor , medicine , pharmacology , biochemistry , immunohistochemistry , receptor
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). 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 that could limit blood flow; however, the increase in PECAM‐1 is consistent with previous reports of DSS‐induced angiogenesis that could decrease flow resistance. Intestinal blood flow measured with microspheres revealed a tendency for a DSS‐induced decrease, indicating that the vasoconstriction may be a more dominant factor than angiogenesis in the overall microvascular resistance. DSS mice given daily 15 mg/kg doses of the endothelin converting enzyme inhibitor SM‐19712 had decreased tissue ET‐1, and a tendency for decreased PECAM‐1. SM‐19712 attenuated histologic signs of tissue injury and inflammation, and decreased the extent of loose stools and fecal blood. However, the inhibitor did not significantly decrease DSS‐induced weight loss, colon shortening, or tissue levels of myeloperoxidase (an indicator of neutrophil infiltration). Supported by Project 2 of NIH P01DK043785.