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

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. 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. 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. 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 microM). These data indicate that 8,15-diHPETE may be a significant endothelium-independent vasodilator product of arachidonate lipoxygenation.