14,15-Dihydroxyeicosatrienoic acid relaxes bovine coronary arteries by activation of KCa channels

William B. Campbell, Christine Deeter, Kathryn M. Gauthier, Richard H. Ingraham, J. R. Falck, Pin Lan Li

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51 Scopus citations

Abstract

Epoxyeicosatrienoic acids (EETs) cause vascular relaxation by activating smooth muscle large conductance Ca2+-activated K+ (KCa) channels. EETs are metabolized to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolase. We examined the contribution of 14,15-DHET to 14,15-EET-induced relaxations and characterized its mechanism of action. 14,15-DHET relaxed U-46619-precontracted bovine coronary artery rings but was approximately fivefold less potent than 14,15-EET. The relaxations were inhibited by charybdotoxin, iberiotoxin, and increasing extracellular K+ to 20 mM. In isolated smooth muscle cells, 14,15-DHET increased an iberiotoxin-sensitive, outward K+ current and increased KCa channel activity in cell-attached patches and inside-out patches only when GTP was present. 14,15-[14C]EET methyl ester (Me) was converted to 14,15-[14C]DHET-Me, 14,15-[14C]DHET, and 14,15-[14C]EET by coronary arterial rings and endothelial cells but not by smooth muscle cells. The metabolism to 14,15-DHET was inhibited by the epoxide hydrolase inhibitors 4-phenylchalcone oxide (4-PCO) and BIRD-0826. Neither inhibitor altered relaxations to acetylcholine, whereas relaxations to 14,15-EET-Me were increased slightly by BIRD-0826 but not by 4-PCO. 14,15-DHET relaxes coronary arteries through activation of KCa channels. Endothelial cells, but not smooth muscle cells, convert EETs to DHETs, and this conversion results in a loss of vasodilator activity.

Original languageEnglish (US)
Pages (from-to)H1656-H1664
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number5 51-5
StatePublished - Jun 29 2002

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Keywords

  • Endothelium-derived hyperpolarizing factor
  • Epoxide hydrolase
  • Epoxyeicosatrienoic acids
  • Potassium channels

ASJC Scopus subject areas

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

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