EET homologs potently dilate coronary microvessels and activate BKCa channels

Yongde Zhang, Christine L. Oltman, Tong Lu, Hon Chi Lee, Kevin C. Dellsperger, Mike Vanrollins

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated the structural specificity of EETs in dilating canine and porcine coronary microvessels (50-140 μm ID) and activating large-conductance Ca2+-activated K+ (BKca) channels. The potencies and efficacies of EET regioisomers and enantiomers were compared with those of two EET homologs: Epoxyeicosaquatraenoic acids (EEQs), which are made from eicosapentaenoic acid by the same cytochrome P-450 epoxygenase that generates EETs from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With ECso values of 3-120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine microvessels. Surprisingly, the EEQs and EDTs had comparable potencies and efficacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BKCa channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BKCa channels possess low structural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyper-polarizing factors.

Original languageEnglish (US)
Pages (from-to)H2430-H2440
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number6 49-6
DOIs
StatePublished - 2001

Keywords

  • Coronary microcirculation
  • Cytochrome P-450 epoxygenases
  • N-3 and n-6 polyunsaturated fatty acids

ASJC Scopus subject areas

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

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