Abstract

The effects of the thromboxane receptor antagonist SQ 30,741 (1 mg/kg) on reflow after thrombolysis and on vasoconstrictor responses to the thromboxane agonist U-46,619 was determined in cynomolgus monkeys. SQ 30,741 (n = 5) or vehicle (n = 4) was administered to anesthetized monkeys upon reocclusion of a stenotic and electrically injured carotid artery, which had been recanalized successfully with streptokinase and heparin. Once blood flow again decreased to zero the treatment was repeated. SQ 30,741 significantly (P less than .05) enhanced reflow by 113% after the first administration and by 150% after the second administration. The respective times to each reocclusion were greater after SQ30,741 (49 +/- 9 and 61 +/- 23 min; P less than .01 and P less than .05) than with vehicle (10 +/- 3 and 15 +/- 2 min). The potency of SQ 30,741 was demonstrated in other anesthetized monkeys by a 8.5 +/- 1.1-fold (n = 3) shift to the right in the U-46,619 dose-response for renal vasoconstriction. The effect of SQ 30,741 (n = 5) on pre-existing renal vasoconstriction was determined using conscious monkeys in which an individually tailored dose of U-46,619 was chosen to sustain an average 82% reduction in blood flow. An arterial injection of SQ 30,741 rapidly returned flow to base-line values, but this antagonism was limited in duration, and flow again reached the nadir within 46 +/- 7 min of continuous U-46,619 infusion. The abbreviated duration of the biological activity of SQ 30,741 in vivo was consistent with its short plasma T1/2 (9.5 +/- 1.3 min; n = 3) determined in separate unanesthetized monkeys by a radioreceptor assay.(ABSTRACT TRUNCATED AT 250 WORDS)