抄録
Stable prostacyclin (PGI2) analogue, beraprost sodium (sodium (±)-(1R*, 2R*, 3aS*, 8bS*)-2, 3, 3a, 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H-cyclopenta [b] benzofuran-5-butyrate, TRK-100) had been reported to inhibit aggregation of platelets and dilate blood vessels. In this report, the effect of beraprost sodium (beraprost) on haemorheological parameters such as erythrocyte deformability and blood viscosity, and activity of blood coagulation system such as activated partial thromboplastin time and prothrombin time were measured in normal rats. Effect of orally administered beraprost on experimentally induced disorders of peripheral circulation such as femoral artery occlusion and venous thrombosis model in rats were assessed.
Erythrocyte deformability was increased by beraprost from the concentration of 23.8 up to 2380nM in vitro (Fig. 1), and from 176 up to 560μg/kg/day after 7 days consecutive administration to normal rats ex vivo (Fig. 2).
Occlusion of rat femoral artery by insertion of polyethylene tube induces reproducible lesions in the toe (Fig. 7) and elevation of blood and plasma viscosity (Tab. 1). Blood viscosity of normal rats was not affected by beraprost up to 10μM in vitro (Fig. 3) or up to 100μg/kg ex vivo (Fig. 4). However, at the dose of 30μg/kg, beraprost normalized blood viscosity of femoral artery occluded rats (Fig. 8).
In the model of stasis induced venous thrombosis, beraprost decreased the weight of thrombus in the inferior vena cava of rats. The effect was dose-dependent at range from 30 to 100μg/kg (Fig. 9). It, however, showed no effects on blood coagulation system of rats ex vivo at the dose which decreased thrombus weight (Fig. 6), and at the concentration range of 23.8nM to 238μM in human plasma in vitro (Fig. 5).
Above results suggest that beraprost may contribute to the improvement of haemorheological impairment and prevention of thrombus formation in the disorder of peripheral circulation.
