Résumé
The effects of dazoxiben on the release of 6-keto-prostaglandin F1?(6-keto-PGF1?) and thromboxane B2(TxB2) in rat neutrophils and 14C-arachidonic acid (14C-AA) metabolization in washed rat platelets were studied.Dazoxiben increased the release of 6-kcto-PGF1? and decreased the release of TxB2 from A23187-stimulated rat neutrophils in a dose-dependent manner in the range of 0.1-5?mol/L drug.The products of 14C-AA metabolism in washed rat platelets wire determined by thin-layer i.adiochromatogra-phy, including thin-layer radio-scanning, autoradiography and liquid scintillation counting.In platelet suspensions stimulated in vitro with 14C-AA, TxB2 and 12-hydro-xy-5, 8,10-heptadecatrienoic acid (HHT) contents were reduced in a doss-dependent manner and a significant redirection of endo-peroxide metabolism to prostaglandin E2, F2?, and D2 was demonstrated after the addition of 0.5~50?mol/L dazoxiben.It is suggested that dazoxiben can inhibit the activity of thromboxane A, synthttases not only in rat platflets but also in rat neutrophils.
Résumé
We studied the effects of the selective thromboxane synthetase inhibitor, dazoxiben (UK-37 248), on the reperfusion arrhythmias induced by ischemia-reperfusion in rats. The results indicated that the administration of dazoxiben (2.5 mg/kg i.v.) 15 min prior to coronary occlusion significantly decreased the incidence of ventricular fibrillation induced by 5 inin ischemia and reperfusion from 11/13 in control to 4/13 in drug-treated (P