Mechanisms of vasorelaxation induced by eicosapentaenoic acid (20:5n‐3) in WKY rat aorta

The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n‐3), the omega‐3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1–100 μ M ) relaxed rat aortae contracted with high K + (80 m M ) or noradrenaline (NA, 1 μ M ) in a concentration‐dependent manner. Contractions induced by Bay K 8644 or increasing concentrations of calcium were unaffected by EPA. The relaxant effect of EPA (3–100 μ M ) was significantly inhibited by indomethacin (10 μ M ), the cyclo‐oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, N ω ‐nitro‐ L ‐arginine methyl ester hydrochloride ( L ‐NAME, 100 μ M ). Removal of the endothelium did not alter EPA‐induced relaxations. In Ca 2+ ‐free, EGTA 2 m M solution, EPA (10–30 μ M significantly inhibited NA‐sustained contractions. Incubation with EPA (5, 10 μ M ) diminished both NA‐induced (1 μ M ) phasic and sustained contractions. The vasorelaxant effects of EPA (30 μ M ) on NA‐induced (1 μ M ) contractions were significantly inhibited by the K + channel blocker, glibenclamide (10 μ M ), but not tetraethylammonium (1 m M ). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA‐induced (1–100 μ M ) responses. These results indicate EPA exerts its endothelium‐independent vasorelaxant effects in WKY rat aortae through production of prostanoids which activate K + ATP channels. Inhibition of Ca 2+ mobilization from intracellular pools and influx through the non‐L‐type, but not the L‐type, Ca 2+ channel are also possible mechanisms action of EPA's.British Journal of Pharmacology (2000) 131 , 1793–1799; doi: 10.1038/sj.bjp.0703754