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 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 microM) 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 microM) was significantly inhibited by indomethacin (10 microM), the cyclo-oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 microM). Removal of the endothelium did not alter EPA-induced relaxations. In Ca(2+)-free, EGTA 2 mM solution, EPA (10 - 30 microM significantly inhibited NA-sustained contractions. Incubation with EPA (5, 10 microM) diminished both NA-induced (1 microM) phasic and sustained contractions. The vasorelaxant effects of EPA (> or =30 microM) on NA-induced (1 microM) contractions were significantly inhibited by the K(+) channel blocker, glibenclamide (10 microM), but not tetraethylammonium (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1 - 100 microM) 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.