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

1 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. 2 Eicosapentaenoic acid (1-100 muM) relaxed rat aortae contracted with high K+ (80 mM) or noradrenaline (NA, 1 muM) in a concentration-dependent manner. Contractions induced by Bay K 8644 or increasing concentrations of calcium were unaffected by EPA. 3 The relaxant effect of EPA (3 - 100 muM) was significantly inhibited by indomethacin (10 muM), the cyclo-oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, N-omega-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 muM). Removal of the endothelium did not alter EPA-induced relaxations. 4 In Ca2+-free, EGTA 2 mM solution, EPA (10-30 muM significantly inhibited NA-sustained contractions. Incubation with EPA (5, 10 muM) diminished both NA-induced (1 muM) phasic and sustained contractions. 5 The vasorelaxant effects of EPA (greater than or equal to 30 muM) on NA-induced (1 muM) contractions were significantly inhibited by the K+ channel blocker, glibenclamide (10 muM), but not tetraethylammonium (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1-100 muM) responses. 6 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.