Contrasting effects of pseudoephedrine and papaverine in dextran sodium sulfate-induced colitis.
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.
Harris
Norman R
NR
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. nharr6@lsuhsc.edu
Specian
Robert D
RD
Carter
Patsy R
PR
Morgan
Georgia A
GA
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000098:blood supply; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010208:Papaverine / Q000008:administration & dosage / Q000627:therapeutic use*; D010973:Platelet Adhesiveness / Q000187:drug effects; D054199:Pseudoephedrine / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014699:Venules
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D054199:Pseudoephedrine; D016264:Dextran Sulfate; D010208:Papaverine