beraprost and Hypercholesterolemia

We evaluated the effects of orally administered beraprost, a stable prostacyclin analogue, on the rheological behavior of red blood cells (RBC) in the presence of hypercholesterolemia. Rabbits fed a cholesterolrich diet were administered various doses of beraprost or pravastatin. We evaluated rheological behavior of RBC by assessing RBC deformability, using a positive-pressure filtration method. The maximum pressure generated by passing a suspension of RBC through a membrane filter was used as an index of RBC deformability. After animals were fed cholesterol for 16 weeks, the maximum pressure increased significantly from 172 +/- 15 mm Hg at baseline to 261 +/- 18 mm Hg (p < 0.01, n = 24). The reduction in RBC deformability associated with hypercholesterolemia improved dose dependently during 1-h incubation with various doses of beraprost. In ex vivo study, beraprost markedly restored RBC deformability 3 h after its oral administration to 218 +/- 17 mm Hg (n = 9) at a low dose and to 215 +/- 20 mm Hg (n = 9) at a high dose. The effect persisted for at least 2 h. Pravastatin failed to reduce the increased maximum pressure. Findings suggest that beraprost treatment may improve the microcirculation by restoring RBC deformability in the presence of hypercholesterolemia.

Topics: Animals; Anticholesteremic Agents; Dose-Response Relationship, Drug; Epoprostenol; Erythrocyte Deformability; Female; Hemorheology; Hypercholesterolemia; Platelet Aggregation Inhibitors; Pravastatin; Rabbits