Activation of vascular BK channels by docosahexaenoic acid is dependent on cytochrome P450 epoxygenase activity

Ru Xing Wang, Qiang Chai, Tong Lu, Hon Chi Lee

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Aimsn-3 Polyunsaturated fatty acids (PUFAs) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochrome P450 (CYP) metabolites of n-3 PUFAs remain virtually unexplored. In this study, we examined the effects of docosahexaenoic acid (DHA) on the regulation of large-conductance calcium-activated potassium (BK) channel activities in coronary arterial smooth muscle cells.Methods and resultsUsing whole-cell patch-clamp techniques, we found that DHA is a potent activator of BK currents in rat coronary arterial smooth muscle cells with an EC50 of 0.23 ± 0.03 M. This effect was abolished by pre-incubation with the CYP epoxygenase inhibitor, SKF525A (10 M). The effects of DHA on the BK channels were reproduced by 16,17-epoxydocosapentaenoic acid (16,17-EpDPE) with an EC50 of 19.7 ± 2.8 nM. The physiological role of the CYP metabolites of DHA was confirmed by measuring DHA-mediated vasodilatation in isolated rat coronary arteries. DHA dilated pressurized isolated coronary arteries in a dose-dependent manner, and the DHA effects were abolished after pre-treatment with SKF525A (10 M) or with iberiotoxin (100 nM). In addition, 16,17-EpDPE directly produced coronary vasodilatation that was iberiotoxin sensitive.ConclusionThese results suggest that DHA-mediated vasodilatation is mediated through CYP epoxygenase metabolites by activation of vascular BK channels.

Original languageEnglish (US)
Pages (from-to)344-352
Number of pages9
JournalCardiovascular research
Volume90
Issue number2
DOIs
StatePublished - May 1 2011

Keywords

  • 16,17-Epoxydocosapentaenoic acid
  • BK channel
  • Coronary arterial smooth muscle cell
  • Cytochrome P450 epoxygenase
  • Docosahexaenoic acid

ASJC Scopus subject areas

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

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