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.
Engler
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University of California San Francisco, Laboratory of Cardiovascular Physiology, Department of Physiological Nursing, 2 Kirkham Street, Room N631, San Francisco, California, CA 94143-0610, USA. mary.engler@nursing.ucsf.edu
Engler
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MM
Browne
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Sun
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Sievers
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D011921:Rats, Inbred WKY; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D026902:Potassium Channel Blockers; D004533:Egtazic Acid; D019789:Tetraethylammonium; D015118:Eicosapentaenoic Acid; D005905:Glyburide; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin