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.
Matsumoto
R
R
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Japan.
Shiroya
T
T
Naka
M
M
Omawari
N
N
Shinomiya
K
K
Fujitani
B
B
Aishita
H
H
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000648:ultrastructure; D020212:Carotid Artery Injuries; D002455:Cell Division; D003250:Constriction; D003505:Cyclodextrins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000648:ultrastructure; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D005070:Evans Blue; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; C051518:OP 41483-alpha-cyclodextrin; D005070:Evans Blue; D011464:Epoprostenol