The vasodilatation induced by hydroperoxy metabolites of arachidonic acid in the rat mesenteric and pulmonary circulation

Open Access
Publisher Website
Google Scholar
Abstract
1 The effects of 15-hydroperoxy metabolites of arachidonic acid on vascular tone were evaluated in the perfused mesenteric preparation, the isolated perfused lung and segments of pulmonary arteries of the rat. 2 In the mesenteric preparation, precontracted with phenylephrine, both 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE, ED50 1.6 nmol) and 8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8,15-diHPETE, ED50 0.3 nmol) induced dose-dependent vasodilatation, whereas 5,15-diHPETE (0.2–100 nmol) had no effect. Prostacyclin (ED50 0.01 nmol) was, however, more potent than the hydroperoxides. 3 In the rat isolated lung, precontracted with the stable thromboxane agonist U-46619, dose-dependent decrease in the perfusion pressure occurred with 15-HPETE (ED50 40 nmol), 5,15-diHPETE (ED50 30 nmol) and 8,15-diHPETE (ED50 7 nmol) while 13-hydroperoxide of linoleic acid had no effect. Prostacyclin was 10 times more potent than 8,15-diHPETE. The vasodilator effects were not affected by indomethacin. 4 In both endothelium intact and denuded rat pulmonary arteries the hydroperoxides 15-HPETE, 8,15-diHPETE, and 5,15-diPETE induced dose-dependent relaxation. The hydroperoxide, 8,15-diHPETE was at least 3 times more potent than 15-HPETE or 5,15-diHPETE. The hydroperoxides had no effect on the basal tone of vessel segments and the relaxation induced by 15-HPETE was not attenuated by methylene blue (5 μm). 5 These data indicate that 8,15-diHPETE may be a significant endothelium-independent vasodilator product of arachidonate lipoxygenation.