EFFECTS OF BERAPROST SODIUM, A STABLE ANALOG OF PROSTACYCLIN, ON HYPERPLASIA, HYPERTROPHY AND GLYCOSAMINOGLYCAN SYNTHESIS OF RAT AORTIC SMOOTH-MUSCLE CELLS

The effects of beraprost sodium, a stable analogue of prostacyclin, on the syntheses of DNA, protein and glycosaminoglycans (GAG) of culture d vascular smooth muscle cells (SMC) were studied. SMC were isolated f rom the thoracic aorta of male Wistar rats. The syntheses of DNA, prot ein and GAG of SMC were determined by incorporations of [H-3]thymidine , [H-3]leucine and [S-35]sulfuric acid, respectively. Insulin at a con centration of 10(-6) M stimulated DNA synthesis 4 fold compared to con trol. Beraprost sodium suppressed the insulin-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppress ed it by 68% at 10(-5) M. Platelet derived growth factor (PDGF) at a c oncentration of 20 ng/ml stimulated DNA synthesis 6 fold compared to c ontrol. Beraprost sodium suppressed the PDGF-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppresse d it by 51% at 10(-5) M. Beraprost sodium suppressed GAG synthesis dos e-dependently at concentrations greater than 10(-7) M and suppressed i t by 49% at 10(-5) M. However, beraprost sodium at concentrations up t o 10(-5) M did not affect protein synthesis. These results indicate th at beraprost sodium suppressed the proliferation and GAG synthesis of SMC but did not affect hypertrophy. Beraprost sodium may be a potent a ntiarteriosclerotic agent through suppression of hyperplasia of SMC an d modification of matrix protein.