Influence of polyunsaturated fatty acids on vasoconstrictions induced by 8-iso-PGF(2alpha) and 8-iso-PGE(2).
8-iso-PGF(2alpha) and 8-iso-PGE(2), 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 A(2) (TP) receptor or a TP-receptor-like isoprostane receptor. Increased levels of 8-iso-PGF(2alpha) 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-gamma-linolenic acid (DGLA) at final concentrations of 3 and 30 micromol/l on vasoconstriction induced by 8-iso-PGF(2alpha), 8-iso-PGE(2) and the thromboxane A(2) mimetic U 46619 in the vasculature of the isolated perfused rabbit ear. Additionally, the effect of indomethacin (final concentration 3 micromol/l) on the effects of the PUFAs was investigated. Our results show that the PUFAs at a concentration of 30 micromol/l caused a significant inhibition of the vasoconstrictions induced by 8-iso-PGF(2alpha), 8-iso-PGE(2) 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 PGE(1), because indomethacin reduced the inhibitory effect of DGLA.
Sametz
W
W
Department of Biomedical Research, University of Graz, Austria. wolfgang.sametz@kfunigraz.ac.at
Jeschek
M
M
Juan
H
H
Wintersteiger
R
R
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D028421:Isoprostanes; D008297:Male; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D028421:Isoprostanes; D014662:Vasoconstrictor Agents; D004281:Docosahexaenoic Acids; C075750:8-epi-prostaglandin F2alpha; D015118:Eicosapentaenoic Acid; D015237:Dinoprost; D015126:8,11,14-Eicosatrienoic Acid; D015232:Dinoprostone; C011987:8-isoprostaglandin E2