Effects of OP-41483.alpha-CD, a stable prostacyclin analog, on cultured endothelial cell dysfunction caused by 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) in vitro

Life Sci. 1993;52(15):1257-64.

Abstract

We studied the effect of OP-41483.alpha-CD, a stable prostacyclin analog, on, 15-HPETE induced bovine endothelial cell dysfunction, which was assessed by measuring a number of endothelial cells attached to plastic plates. 15-HPETE decreased the number of attached endothelial cells in a concentration- and time-dependent manner. OP-41483.alpha-CD and PGI2 significantly inhibited 15-HPETE induced dysfunction of the cells at a concentration of more than 10(-9)M. Besides, DDA (10(-6) - 10(-4)M) an adenylate cyclase inhibitor, diminished the inhibitory effect of OP-41483.alpha-CD on 15-HPETE induced cell dysfunction in a concentration-dependent manner. Furthermore, OP-41483.alpha-CD increased cAMP levels in the endothelial cells in the range of 10(-10) to 10(-8)M in a dose-dependent manner. These data suggest that OP-41483.alpha-CD could exert an inhibitory action on 15-HPETE induced endothelial cell dysfunction via partly increasing its effect on the intracellular cAMP level.

MeSH terms

  • Alprostadil / analogs & derivatives
  • Alprostadil / pharmacology
  • Animals
  • Cattle
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclodextrins / pharmacology*
  • Cyclodextrins / therapeutic use
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology
  • Epoprostenol / therapeutic use
  • Leukotrienes / pharmacology
  • Lipid Peroxides / pharmacology
  • Peripheral Vascular Diseases / drug therapy
  • Vasoconstrictor Agents / pharmacology
  • alpha-Cyclodextrins*

Substances

  • Cyclodextrins
  • Leukotrienes
  • Lipid Peroxides
  • Vasoconstrictor Agents
  • alpha-Cyclodextrins
  • prostaglandin E1-alpha-cyclodextrin
  • OP 41483-alpha-cyclodextrin
  • 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid
  • Epoprostenol
  • Cyclic AMP
  • Alprostadil