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 cyclooxygenase pathways in neutrophils and platelets may be involved in the pathophysiological response to arterial injury in vivo. Therefore, we investigated the effects of 3-amino-1-[m(trifluoromethyl)phenyl]-2-pyrazoline (BW755C), a dual lipoxygenase/cyclooxygenase inhibitor, on mural platelet and neutrophil deposition, and the vasoconstrictive response that followed carotid arterial injury by angioplasty in pigs. 51Cr platelet deposition at the site of deep arterial wall injury averaged 55.4 +/- 12.2 x 10(6)/cm2 in the vehicle-treated group (n = 10). BW755C (10 mg/kg i.v., n = 10) significantly reduced this mural platelet deposition by more than 50% to 25.4 +/- 5.3 x 10(6)/cm2 (P < .05) and decreased 111In neutrophil deposition from 240.6 +/- 30.4 x 10(3)/cm2 in the control group to 114.4 +/- 20.4 x 10(3)/cm2 (P < .005) in the treated group. BW755C had no hemodynamic effects. However, the angiographic vasoconstrictive response at the site of endothelial injury distally was significantly attenuated by the dual inhibitor from 45.4 +/- 2.6% to 29.7 +/- 4.3% (P < .005). These beneficial effects of BW755C were 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 the dual lipoxygenase/cyclooxygenase inhibitor BW755C prevents the acute thrombotic and vasomotor responses related to arterial injury by angioplasty, predominantly through inhibition of neutrophil function.
Provost
P
P
Laboratory of Thrombosis and Atherosclerosis, Montreal Heart Institute, Quebec, Canada.
Merhi
Y
Y
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology*; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D013481:Superoxides; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine