Role of leukotrienes on coronary vasoconstriction in isolated hearts of arthritic rats: Effect of in vivo treatment with Cl-986, a dual inhibitor of cyclooxygenase and lipoxygenase

In this study, coronary perfusion pressure and force of contraction were in vestigated in isolated hearts removed from arthritic rats by using the Lang endorff method. A strong coronary vasoconstriction was determined in arthri tic hearts which was associated with elevated levels of arachidonate 5-lipo xygenase (5-LOX) products, leukotriene B-4 (LTB4) and LTC4 in coronary effl uents. In vivo treatment with the dual inhibitor of cyclooxygenase (COX) an d LOX, CI-986 (2 and 10 mg/kg/day) on days 14-26 following adjuvant injecti on, prevented the coronary vasoconstriction and the increased production of LTB4 and LTC4. These results suggest that the coronary vasoconstriction in the isolated arthritic hearts is associated with an increased activity of the LOX system and CI-986 could have a preventive effect on constriction of coronary arteries. Copyright (C) 2000 S. Karger AG, Basel.