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The vasodilatation induced by hydroperoxy metabolites of arachidonic acid in the rat mesenteric and pulmonary circulation
Author(s) -
D'Alarcao Marc,
Corey E. J.,
Cunard Cynthia,
Ramwell Peter,
Uotila Pekka,
Vargas Roberto,
Wroblewska Barbara
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11256.x
Subject(s) - vasodilation , ed50 , prostacyclin , mesenteric arteries , arachidonic acid , phenylephrine , thromboxane a2 , chemistry , endocrinology , thromboxane , vasoconstriction , medicine , endothelium , pharmacology , biochemistry , in vitro , artery , blood pressure , platelet , receptor , enzyme
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, ED 50 1.6 nmol) and 8,15‐dihydroperoxy‐5,9,11,13‐eicosatetraenoic acid (8,15‐diHPETE, ED 50 0.3 nmol) induced dose‐dependent vasodilatation, whereas 5,15‐diHPETE (0.2–100 nmol) had no effect. Prostacyclin (ED 50 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 (ED 50 40 nmol), 5,15‐diHPETE (ED 50 30 nmol) and 8,15‐diHPETE (ED 50 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 μ m ). 5 These data indicate that 8,15‐diHPETE may be a significant endothelium‐independent vasodilator product of arachidonate lipoxygenation.