SQ-29,548, a newly synthetized thromboxane receptor antagonist, was investigated for its effects on platelet and vascular thromboxane receptors in vivo and in vitro. Arachidonic acid (AA)-induced sudden death in rabbits was dose-dependently inhibited by SQ-29,548 at doses ranging from 0.2 to 2 mg/kg. Sudden death was accompanied by a 46 +/- 6% decrease in continuously measured circulating platelet count, which was also dose-dependently inhibited by SQ-29,548. The AA-induced increase in continuously recorded whole blood ATP content was 1.2 +/- 0.4 microM and was significantly diminished by all SQ-29,548 doses used. Platelet aggregation induced by AA, the endoperoxide analog U-46,619 or collagen in platelet-rich plasma was dose-dependently inhibited by SQ-29,548 which exerted an IC50 of 0.8, 0.3 or 2.9 microM, respectively. In contrast, ADP and platelet-activating factor acether-induced platelet aggregation were unaffected at concentrations of SQ-29,548 up to 260 microM. Thromboxane B2 formation was not significantly altered by SQ-29,548 (1-100 microM) in platelet-rich plasma stimulated with AA or in spontaneously clotting whole blood. Thromboxane synthetase, cyclooxygenase and lipoxygenase product formation were unaffected by SQ-29,548 when washed rabbit platelets were stimulated with radiolabeled AA and the products were measured after separation by thin-layer chromatography. U-46,619 (500 nM), carbocyclic thromboxane A2 (15 nM) and prostaglandin F2 alpha (3 microM)-induced contractions of rabbit pulmonary artery were antagonized by SQ-29,548 exerting a IC50 value between 120 and 40 nM, whereas norepinephrine-induced contractions were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)