ABSTRACT
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
ABSTRACT
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.