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 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.


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.


CONCLUSIONS
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.
Panés
J
J
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Russell
J M
JM
Wolf
R E
RE
Wallace
J L
JL
Granger
D N
DN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D020024:Leukotriene Antagonists; D008297:Male; D000078183:Oxindoles; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D014699:Venules / Q000187:drug effects; D002722:Chlorobenzenes
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D007213:Indomethacin; D020024:Leukotriene Antagonists; D000078183:Oxindoles; D010972:Platelet Activating Factor; C060893:MK-886; D002722:Chlorobenzenes; C062866:tenidap