Prolongation of Rat Tail Bleeding Time Caused by Oral Doses of a Thromboxane Synthetase Inhibitor Which Have Little Effect on Platelet Aggregation

Abstract

N (7-carboxyheptyl) imidazole is an inhibitor of platelet thromboxane synthetase that has no effect on the cyclooxygenase activity. An oral dose of the substance to rats (10 mg/kg) prolonged tail bleeding time from 170 +/- 13 sec to 284 +/- 22 sec. This oral dose also inhibited platelet thromboxane B2 production induced by collagen ex vivo but had little effect on the aggregation dose response curve. There was no effect on thrombin-induced aggregation. Neither the thrombocytopenia induced by the Arthus reaction nor thrombus formation on an implanted cotton thread were inhibited by oral doses of carboxyheptylimidazole up to 30 mg/kg. Similarly neither the prothrombin nor activated partial thromboplastin time were affected. It is postulated that this thromboxane synthetase inhibitor prolongs bleeding time nor by inhibiting platelet aggregation or blood coagulation but rather by preventing the vasoconstriction which would normally be caused by thromboxane A2.