EFFECTS OF TENIDAP ON LEUKOCYTE-ENDOTHELIAL CELL-ADHESION IN MESENTERIC VENULES

Objective, To compare the proinflammatory effects of tenidap to those of indomethacin, and to assess the influence of lipoxygenase inhibition with either a leukotriene synthesis inhibitor (L663,536) or tenidap on platelet activating factor (PAF) induced leukocyte adhesion. Methods. Adherent leukocytes, emigrated leukocytes, number of rolling leukocytes/100 mu m venule, flux of rolling leukocytes, and leukocyte rolling velocity were quantitated in mesenteric venules (25-35 mu m diameter and > 150 mu m length) of Sprague-Dawley rats using intravital microscopy. In,some experiments, the mesentery was superfused with indomethacin (25 mu g/ml), tenidap (30 mu g/ml), or both drugs simultaneously. In other experiments the mesentery was superfused with PAF 100 nM and the effects of treatment with 1,663,536 (Ip mg/kg given orally) or superfusion with tenidap were determined. Results, Indomethacin significantly increased leukocyte rolling and adhesion. Tenidap did not promote leukocyte-endothelial cell adhesion and blocked the increased leukocyte rolling and adhesion promoted by indomethacin. Both L663,536 and tenidap significantly attenuated PAF induced leukocyte-endothelial cell adhesion. Conclusion, Tenidap does not exhibit the proinflammatory properties of indomethacin. The reduction of indomethacin or PAF induced leukocyte-endothelial :cell adhesion by tenidap appeared to result from its lipoxygenase inhibitory activity. Modulation of leukocyte-endothelial cell adhesion may be a never mechanism of the antiinflammatory activity of tenidap and may reduce the relative risk of gastric ulceration with tenidap.