8-iso-PGF2α and 8-iso-PGE2, which are released in vivo by free radical catalyzed peroxidation of arachidonic acid, are equipotent vasoconstrictors in vivo and in vitro. It is assumed that they exert this effect via activation of the thromboxane A2 (TP) receptor or a TP-receptor-like isoprostane receptor. Increased levels of 8-iso-PGF2α have been detected in human cardiovascular diseases. It has been found that polyunsaturated fatty acids (PUFAs) have many beneficial effects in cardiovascular diseases, including antivasoconstrictor actions. Therefore, we investigated the influence of perfusions with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-γ-linolenic acid (DGLA) at final concentrations of 3 and 30 μmol/l on vasoconstriction induced by 8-iso-PGF2α, 8-iso-PGE2 and the thromboxane A2 mimetic U 46619 in the vasculature of the isolated perfused rabbit ear. Additionally, the effect of indomethacin (final concentration 3 μmol/l) on the effects of the PUFAs was investigated. Our results show that the PUFAs at a concentration of 30 μmol/l caused a significant inhibition of the vasoconstrictions induced by 8-iso-PGF2α, 8-iso-PGE2 and U 46619. Furthermore, it can be assumed that a part of the inhibitory effect of DGLA is due to the effect of a cyclooxygenase product, probably PGE1, because indomethacin reduced the inhibitory effect of DGLA.
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