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

Megumu Fukunaga, Takafumi Yura, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

8-Epi-prostaglandin F(8-epi-PGF) 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-PGFindicated the existence of two distinct binding sites. The Kdvalues were similar to those of cultured rat aortic smooth-muscle cells, suggesting that the high- and the low-affinity binding sites represent isoprostane and TxA2receptors, respectively. 8-Epi-PGFdose-dependently stimulated endothelin-1 (ET-1) secretion from BAECs. These increases were partially inhibited by a TxA2receptor antagonist, consistent with the premise that isoprostanes and TxA2recognize 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-PGFmay help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGFin patients with hepatorenal syndrome.

Original languageEnglish (US)
Pages (from-to)S51-S52
JournalJournal of Cardiovascular Pharmacology
Volume26
StatePublished - 1995
Externally publishedYes

Keywords

  • Endothelin-1 secretion
  • F<inf>2</inf>-isoprostane
  • Hepatorenal syndrome
  • Isoprostane receptor
  • Thromboxane A<inf>2</inf>

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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