BW755C, A DUAL LIPOXYGENASE CYCLOOXYGENASE INHIBITOR, REDUCES MURAL PLATELET AND NEUTROPHIL DEPOSITION AND VASOCONSTRICTION AFTER ANGIOPLASTY INJURY IN PIGS

Arachidonic acid metabolism through the lipoxygenase and cyclooxygenas e pathways in neutrophils and platelets may be involved in the pathoph ysiological response to arterial injury in vivo. Therefore, we investi gated the effects of 3-amino-1-[m(trifluoromethyl)phenyl]-2-pyrazoline (BW755C), a dual lipoxygenase/cyclooxygenase inhibitor, on mural plat elet and neutrophil deposition, and the vasoconstrictive response that followed carotid arterial injury by angioplasty in pigs. Cr-51 platel et deposition at the site of deep arterial wall injury averaged 55.4 /- 12.2 x 10(6)/cm(2) in the vehicle-treated group (n = 10). BW755C (1 0 mg/kg i.v., n = 10) significantly reduced this mural platelet deposi tion by more than 50% to 25.4 +/- 5.3 x 10(6)/cm(2) (P < .05) and decr eased In-111 neutrophil deposition from 240.6 +/- 30.4 x 10(3)/cm(2) i n the control group to 114.4 +/- 20.4 x 10(3)/cm(2) (P < .005) in the treated group. BW755C had no hemodynamic effects. However, the angiogr aphic vasoconstrictive response at the site of endothelial injury dist ally was significantly attenuated by the dual inhibitor from 45.4 +/- 2.6% to 29.7 +/- 4.3% (P < .005). These beneficial effects of BW755C w ere associated with inhibition of neutrophil-mediated but not platelet -mediated whole-blood aggregation and with a significant reduction in neutrophil superoxide anion generation. These results indicate that th e dual lipoxygenase/cyclooxygenase inhibitor BW755C prevents the acute thrombotic and vasomotor responses related to arteria! injury by angi oplasty, predominantly through inhibition of neutrophil function.