Contrasting effects of pseudoephedrine and papaverine in dextran sodium sulfate-induced colitis.

Abstract

BACKGROUND: Dextran sodium sulfate (DSS) induces submucosal arteriolar constriction that reduces blood flow to the intestine, and the relevance of this decrease in flow needs further investigation. In the present study we examined the effects of a vasoconstrictor (pseudoephedrine) and a vasodilator (papaverine) on the outcome of DSS-induced colitis. METHODS: Mice were given DSS in drinking water for 6 days, with enemas on days 0, 1, 3, and 5 containing pseudoephedrine, papaverine, or no drug. At the conclusion of the 6-day protocol a disease activity index comprising weight loss, stool consistency, and rectal bleeding was evaluated, along with intravital microscopy observations of submucosal venular leukocyte and platelet adherence in the proximal colon and terminal ileum. RESULTS: Pseudoephedrine and papaverine had several contrasting effects on the outcome of DSS ingestion: pseudoephedrine induced the highest levels of weight loss, loose stools, venular platelet adherence, and overall disease activity index, while papaverine induced the highest levels of venular leukocyte adherence, but the lowest levels of rectal bleeding, loose stools, and overall disease activity index. CONCLUSIONS: The results suggest that vasoconstriction worsens the pathological consequences of DSS in the mouse model of colitis.