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 μM) relaxed rat aortae contracted with high K+ (80 mM) or noradrenaline (NA, 1 μM) 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 μM) was significantly inhibited by indomethacin (10 μM), the cyclo-oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM). Removal of the endothelium did not alter EPA-induced relaxations. In Ca2+-free, EGTA 2 mM solution, EPA (10–30 μM significantly inhibited NA-sustained contractions. Incubation with EPA (5, 10 μM) diminished both NA-induced (1 μM) phasic and sustained contractions. The vasorelaxant effects of EPA (30 μM) on NA-induced (1 μM) contractions were significantly inhibited by the K+ channel blocker, glibenclamide (10 μM), but not tetraethylammonium (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1–100 μM) 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 Ca2+ mobilization from intracellular pools and influx through the non-L-type, but not the L-type, Ca2+ channel are also possible mechanisms action of EPA's. British Journal of Pharmacology (2000) 131, 1793–1799; doi:10.1038/sj.bjp.0703754