Effect of OP-41483.alpha-CD, a prostacyclin analog, on a clamp-induced endothelial injury in rats

We studied the effect of OP-41483.alpha-CD, a stable prostacyclin analog, on clamp-induced endothelial injury in rats. The injury was assessed by vascular Evans blue leakage and using a scanning electron microscope. OP-41483.alpha-CD significantly reduced the Evans blue leakage at doses of 30 and 100 ng/kg/min. PGE1.CD was also found to show an equipotent inhibitory action on the dye leakage. From scanning electron microscopic observations, a moderate degree of intimal defects, microvillous projections and platelet adhesions at the luminal surface were seen in the specimens from OP-41483.alpha-CD (30 and 100 ng/kg/min) treated rats. Furthermore, OP-41483.alpha-CD, PGE1.CD and Dibutyryl cyclic AMP (DbcAMP) were found to accelerate a proliferation of cultured bovine endothelial cells in a dose-dependent manner in vitro. Taken together, these data indicate that the endothelial regenerative effect of OP-41483.alpha-CD could contribute to healing of clamp-induced endothelial injury and it may be an important therapeutic drug to protect vascular intimal injury.