The role of endothelial cells in the relaxations induced by 13-hydroxy- and 13-hydroperoxylinoleic acid in canine arteries.

Abstract

1. One of the major fatty acids in the arterial wall is linoleic acid. It has been shown that its 13-hydroxy metabolite (13-HODE) is generated in significant amounts by cultured endothelial cells. The aim of the present study was to investigate the relaxations to 13-HODE and its hydroperoxyprecursor (13-HPODE) and to examine the role of the endothelial cells. 2. Ring segments of canine circumflex and splenic artery were mounted in organ chambers for isometric tension recording. During contractions induced by prostaglandin F2 alpha or noradrenaline, 13-HODE and 13-HPODE evoked dose-dependent relaxations. Removal of the endothelial cells reduced the relaxations to 13-HODE, but had no effect on those elicited by 13-HPODE. 3. Indomethacin and meclofenamate (0.3 microM to 30 microM) blocked the relaxations evoked by 13-HODE and 13-HPODE in endothelium-denuded rings. In segments with endothelium, both cyclo-oxygenase inhibitors again abolished the relaxations to 13-HODE, but only diminished those to 13-HPODE. 4. Prostacyclin biosynthesis, as measured by radioimmunoassay, increased upon incubation with 13-HODE and 13-HPODE (10 microM). Bioassay of the release of nitric oxide (NO) indicated that NO was not involved in the relaxations elicited by either metabolite. Moreover, L-NG-nitroarginine (100 microM), a specific inhibitor of NO synthesis, did not influence the relaxations to 13-HODE and 13-HPODE. The responses to 13-HPODE were also not altered by superoxide dismutase. 5. In the splenic artery 13-HPODE and 13-HODE induced contractions above 3 microM which were blocked by the thromboxane receptor antagonist, daltroban.In the circumflex artery contractile responses to high concentrations of 13-HODE could be observed only after inhibition of cyclo-oxygenase.6. We conclude that the vasodilatation induced by 13-HODE and 13-HPODE was due to stimulation of prostacyclin biosynthesis both in the endothelium and smooth muscle cells or other subendothelial structures. An additional, unidentified intermediate, which was neither NO nor a cyclo-oxygenase product nor superoxide anion, contributed to the relaxations to 13-HPODE in arteries with endothelium.