Relaxing effects of 15-lipoxygenase products of arachidonic acid on rat aorta.
In the presence of indomethacin, arachidonic acid relaxes precontracted rings of rat aorta only when the endothelium is intact. Arachidonate-induced, endothelium-dependent relaxation is potentiated by superoxide dismutase. In contrast, linoleic acid (LA) contracts endothelium-intact and -denuded rings. Arachidonate is metabolized in endothelial cells by both cyclo-oxygenase and 15-lipoxygenase. Therefore, we determined the vasodilatory effect of 15-lipoxygenase products. The products generated by soybean lipoxygenase (SLO) from arachidonate in the bioassay bath relax precontracted, de-endothelialized ring segments of rat aorta. This relaxation is potentiated by superoxide dismutase and is more prominent when high concentrations of SLO are used. The main metabolites recovered from the bioassay bath were 5,15-dihydroperoxyeicosatetraenoic acid and 8,15-dihydroperoxyeicosatetraenoic acid. At lower concentrations of SLO the degree of relaxation is less and the major product is 15-hydroperoxyeicosatetraenoic acid. LA is metabolized by SLO to 13-hydroperoxyoctadecadienoic acid. The relaxation induced by the incubation of LA with SLO in endothelium-denuded rings is less than that obtained with arachidonic acid. In endothelium-denuded rings that were precontracted with phenylephrine authentic 15-hydroperoxyeicosatetraenoic acid did not induce clear effect (at 40 microM 15-hydroperoxide caused relaxation, whereas at 15 microM induced small contraction) and 13-hydroperoxyoctadecadienoic acid of LA induced contraction. Neither 5,15-dihydroperoxyeicosatetraenoic acid nor 8,15-dihydroperoxyoctadecadienoic acid (1-15 microM) induced a well defined relaxation. This study indicates that arachidonic acid is metabolized by SLO to a vasodilatory compound(s) that is possibly derived from 15-hydroperoxyeicosatetraenoic acid.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology*; D001091:Arachidonate Lipoxygenases / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology*; D004727:Endothelium / Q000502:physiology; D015289:Leukotrienes; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D001095:Arachidonic Acids; D015289:Leukotrienes; D008041:Linoleic Acids; D008054:Lipid Peroxides; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D019787:Linoleic Acid; D001091:Arachidonate Lipoxygenases; D001093:Arachidonate 15-Lipoxygenase; D013482:Superoxide Dismutase