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 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. 3. 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, N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM). Removal of the endothelium did not alter EPA-induced relaxations. 4. 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. 5. 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 tetraethylammoniam (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1-100 μM) 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.