Docosahexanoic Acid-Induced Coronary Arterial Dilation: Actions of 17S-Hydroxy Docosahexanoic Acid on K+ Channel Activity

doi:10.1124/jpet.110.176461

Paper

Docosahexanoic Acid-Induced Coronary Arterial Dilation: Actions of 17S-Hydroxy Docosahexanoic Acid on K+ Channel Activity

Published Mar 1, 2011 · Xiang Li, Song Hong, Pin-Lan Li

Journal of Pharmacology and Experimental Therapeutics

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27

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Abstract

Despite extensive studies, the mechanisms mediating the cardiovascular actions of ω-3 polyunsaturated fatty acids has not yet been fully understood. The present study determined the possible actions of an endothelium-derived lipoxygenase product of docosahexanoic acid (DHA), 17S-hydroxy DHA (17S-HDHA), in bovine coronary arteries. High-performance liquid chromatography (LC) analysis demonstrated that bovine coronary arterial endothelial cells can metabolize DHA via lipoxygenases, and one of the major products was confirmed to be 17S-HDHA by LC-tandem mass spectrometry. In isolated perfused small bovine coronary arteries, 17S-HDHA (10−9 to 10−5 M) caused a concentration-dependent dilation with a maximum dilator response of 87.8 ± 2.5%, which is much more potent than the dilator response of its precursor, DHA. Moreover, 17S-HDHA-induced vasodilatations were significantly blocked by iberiotoxin, a large conductance Ca2+-activated K+ (BKCa) channel blocker, but not altered by an ATP-sensitive K+ channel blocker, glibenclamide. In patch-clamp whole-cell recording, 17S-HDHA markedly increased K+ currents in coronary arterial smooth muscle cells. In the inside-out mode, but not in the cell-attached mode, 17S-HDHA dramatically increased the BKCa channel activity, which was substantially blocked by iberiotoxin. Collectively, our findings indicate that 17S-HDHA, an endothelium-derived DHA product via lipoxygenase, activates BKCa channels in coronary arterial smooth muscle cells, leading to coronary vasodilation, which may represent an important mechanism mediating the beneficial actions of DHA in coronary circulation.

In Vitro Study

Study Snapshot

17S-HDHA, an endothelium-derived DHA product, activates BKCa channels in coronary arterial smooth muscle cells, leading to coronary vasodilation, potentially mediating the beneficial actions of DHA in coronary circulation.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Docosahexanoic Acid-Induced Coronary Arterial Dilation: Actions of 17S-Hydroxy Docosahexanoic Acid on K+ Channel Activity

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Citations

15-Hydroxyeicosatrienoic acid induces nasal congestion by changing vascular functions in mice.

15-HETrE, found in allergic rhinitis patients, can exacerbate nasal congestion by stimulating prostaglandin D2 and IP receptors, leading to dilation of nasal mucosal vasculature.

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