Epoxide hydrolases regulate epoxyeicosatrienoic acid incorporation into coronary endothelial phospholipids

Neal L. Weintraub, Xiang Fang, Terry L. Kaduce, Mike VanRollins, Papri Chatterjee, Arthur A. Spector

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Cytochrome P-450-derived epoxyeicosatrienoic acids (EETs) are avidly incorporated into and released from endothelial phospholipids, a process that results in potentiation of endothelium-dependent relaxation. EETs are also rapidly converted by epoxide hydrolases to dihydroxyeicosatrienoic acid (DHETs), which are incorporated into phospholipids to a lesser extent than EETs. We hypothesized that epoxide hydrolases functionally regulate EET incorporation into endothelial phospholipids. Porcine coronary artery endothelial cells were treated with an epoxide hydrolase inhibitor, 4- phenylchalcone oxide (4-PCO, 20 μmol/l), before being incubated with 3H- labeled 14,15-EET (14,15-[3H]EET). 4-PCO blocked conversion of 14,15-[3H] EET to 14,15-[3H]DHET and doubled the amount of radiolabeled products incorporated into cell lipids, with >80% contained in phospholipids. Moreover, pretreatment with 4-PCO before incubation with 14,15[3H]EET enhanced A-23187-induced release of radiolabeled products into the medium. In contrast, 4-PCO did not alter uptake, distribution, or release of [3H]arachidonic acid. In porcine coronary arteries, 4-PCO augmented 14,15- EET-induced potentiation of endothelium-dependent relaxation to bradykinin. These data suggest that epoxide hydrolases may play a role in regulating EET incorporation into phospholipids, thereby modulating endothelial function in the coronary vasculature.

Original languageEnglish (US)
Pages (from-to)H2098-H2108
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number5 46-5
DOIs
StatePublished - Nov 1999

Keywords

  • Arachidonic acid
  • Cytochrome P-450
  • Dihydroxyeicosatrienoic acids
  • Porcine coronary artery

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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