Stimulatory effect of 8-Epi-PGF2 alpha, an F2-isoprostane, on endothelin-1 release

J Cardiovasc Pharmacol. 1995;26 Suppl 3:S51-2.

Abstract

8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane produced in vivo by a cyclooxygenase-independent, free radical-catalyzed lipid peroxidation mechanism. It exhibits renal vasoconstrictor effects by binding to a receptor related to, but distinct from, that of thromboxane A2 (TxA2). In cultured bovine aortic endothelial cells (BAECs), competitive binding assays using [3H]-8-epi-PGF2 alpha indicated the existence of two distinct binding sites. The Kd values were similar to those of cultured rat aortic smooth-muscle cells, suggesting that the high- and the low-affinity binding sites represent isoprostane and TxA2 receptors, respectively. 8-Epi-PGF2 alpha dose-dependently stimulated endothelin-1 (ET-1) secretion from BAECs. These increases were partially inhibited by a TxA2 receptor antagonist, consistent with the premise that isoprostanes and TxA2 recognize closely related receptors. The presence of specific binding sites for F2-isoprostanes on endothelial cells widens the scope of the possible pathophysiologic significance of these eicosanoids, released during oxidant injury, to include alteration of endothelial cell biology. The release of ET-1 by 8-epi-PGF2 alpha may help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGF2 alpha in patients with hepatorenal syndrome.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cattle
  • Cells, Cultured
  • Dinoprost / analogs & derivatives*
  • Dinoprost / metabolism
  • Dinoprost / pharmacology
  • Endothelins / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Rats
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Endothelins
  • Vasoconstrictor Agents
  • 8-epi-prostaglandin F2alpha
  • Dinoprost