Effects of tenidap on leukocyte-endothelial cell adhesion in mesenteric venules

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.

Adherent leukocytes, emigrated leukocytes, number of rolling leukocytes/100 microns venule, flux of rolling leukocytes, and leukocyte rolling velocity were quantitated in mesenteric venules (25-35 microns diameter and > 150 microns length) of Sprague-Dawley rats using intravital microscopy. In some experiments, the mesentery was superfused with indomethacin (25 micrograms/ml), tenidap (30 micrograms/ml), or both drugs simultaneously. In other experiments the mesentery was superfused with PAF 100 nM and the effects of treatment with L663,536 (10 mg/kg given orally) or superfusion with tenidap were determined.

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.

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 novel mechanism of the antiinflammatory activity of tenidap and may reduce the relative risk of gastric ulceration with tenidap.