Venular constriction of submucosal arterioles induced by dextran sodium sulfate

Background: Leukocyte and platelet adherence in postcapillary venules has been speculated to induce constriction of closely paired arterioles. This mechanism was investigated in the current study, in a model of intestinal inflammation induced by dextran sodium sulfate (DSS; 5,000 molecular weight). Methods: Closely paired, parallel arterioles and venules in the submucosa of the mouse intestine were observed using fluorescent intravital microscopy. Arterioles in control mice were compared to arterioles in mice given 5% DSS in drinking water for 11 days. Results: DSS induced an inflammatory response in which fluorescently labeled leukocytes and platelets were observed adhering to venules. Arterioles constricted and flow decreased significantly when the arterioles were paired with venules having adherent leukocytes and platelets, although the decreases in flow and diameter appeared to be more dependent on platelet than leukocyte adherence. No significant constriction was observed in arterioles paired with venules having minimal platelet adherence. Inhibition of thromboxane with 100 mg/kg ozagrel induced a significant dilation of arterioles in DSS mice that was absent in control mice. Conclusion: The results are consistent with a proposed mechanism in which thromboxane constricts submucosal arterioles when the arterioles are closely paired with platelet‐bearing venules in DSS‐induced inflammation.