20-Hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries

Bruno Escalante, Ken Omata, William Sessa, Sang Gyeong Lee, J R Falck, Michal Laniado Schwartzman

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Abstract

Recently we have demonstrated that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) constricts rat aortic rings and that this effect is cyclooxygenase- and endothelium-dependent. Incubation of 20-HETE with ram seminal vesicles, a rich source of cyclooxygenase, led to the identification of vasoconstrictor metabolites, the 20-hydroxy-endoperoxides. In the present study, we demonstrated differences in the potency of 20-HETE to constrict several arteries. In all blood vessels tested, the 20-HETE contractile effect was cyclooxygenase- and endothelium-dependent. Differences in contractile potency of 20-HETE varied according to the blood vessels; potency being higher in more muscular arteries than elastic ones. Furthermore, 20-HETE was more potent in eliciting vasoconstriction than its precursor, arachiddonic acid. We also provide evidence for the generation of 20-hydroxy-endoperoxides from 20-HETE by the endothelial cyclooxygenase. 20-HETE is a major arachidonate metabolite formed by the cytochrome P450 monooxygenases in rat, human and rabbit kidneys. In addition, blood cells such as leukocytes have the ability to produce 20-HETE, suggesting its presence in the circulation. Furthermore, 20-HETE has been shown to inhibit platelet aggregation. Thus, the ability of 20-HETE to modulate vascular tone and platelet function implicates a role for this compound in the regulation of hemostasis.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalEuropean Journal of Pharmacology
Volume235
Issue number1
DOIs
StatePublished - Apr 22 1993

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Keywords

  • 20-HETE (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
  • Arachidonic acid
  • Cytochrome P450
  • Endothelium-dependent vasoconstrictor

ASJC Scopus subject areas

  • Pharmacology

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