Potentiation of endothelium-dependent relaxation by epoxyeicosatrienoic acids

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Abstract

Epoxyeicosatrienoic acids (EETs) are potent endothelium-derived vasodilators formed from cytochrome P-450 metabolism of arachidonic acid. EETs and their diol products (DHETs) are also avidly taken up by endothelial cells and incorporated into phospholipids that participate in signal transduction. To investigate the possible functional significance of EET and DHET incorporation into cell lipids, we examined the capacity of EETs and DHETs to relax porcine coronary arterial rings and determined responses to bradykinin (which potently activates endothelial phospholipases) before and after incubating the rings with these eicosanoids. 14,15-EET and 11,12-EET (5 μmol/L) produced 75±9% and 52±4% relaxation, respectively, of U46619- contracted rings, whereas 8,9-EET and 5,6-EET did not produce significant relaxation. The corresponding DHET regioisomers produced comparable relaxation responses. Preincubation with 14,15-EET, 11,12-EET, 14,15-DHET, and 11,12-DHET augmented the magnitude and duration of bradykinin-induced relaxation, whereas endothelium-independent relaxations to aprikalim and sodium nitroprusside were not potentiated. Pretreatment with 2 μmol/L triacsin C (an inhibitor of acyl coenzyme A synthases) inhibited [3H]14,15- EET incorporation into endothelial phospholipids and blocked 11,12-EET- and 14,15-DHET-induced potentiation of relaxation to bradykinin. Exposure of [3H]14,15-EET-labeled endothelial cells to the Ca2+ ionophore A23187 (2 μmol/L) resulted in a 4-fold increased release of EET and DHET into the medium. We conclude that incorporation of EETs and DHETs into cell lipids results in potentiation of bradykinin-induced relaxation in porcine coronary arteries, providing the first evidence that incorporated EETs and DHETs are capable of modulating vascular function.

Original languageEnglish (US)
Pages (from-to)258-267
Number of pages10
JournalCirculation Research
Volume81
Issue number2
StatePublished - 1997
Externally publishedYes

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Keywords

  • Acyl coenzyme A synthase
  • Arachidonic acid
  • Dihydroxyeicosatrienoic acid
  • Epoxyeicosatrienoic acid
  • Porcine coronary artery

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Weintraub, N. L., Fang, X., Kaduce, T. L., Vanrollins, M., Chatterjee, P., & Spector, A. A. (1997). Potentiation of endothelium-dependent relaxation by epoxyeicosatrienoic acids. Circulation Research, 81(2), 258-267.