Vascular interaction between 5-hydroxytryptamine and 15-lipoxygenase metabolites of arachidonic acid.
In isolated canine saphenous veins, the contractions elicited by the 15-lipoxygenase metabolites 15-HETE and 15-HPETE were augmented by 5-hydroxytryptamine (5-HT) in a concentration-dependent way. This potentiation was not mediated by the endothelium nor was it influenced by the 5-HT2-antagonist ketanserin. Phentolamine, however, reduced both the contractions and the potentiation by 5-HT. These data provide evidence for a receptor-mediated potentiation by 5-HT which occurs independently of 5-HT2-receptors. The interaction between 5-HT or aggregating platelets and 15-HPETE was studied in isolated rabbit brachiocephalic arteries. Threshold concentrations of 5-HT and platelets markedly potentiated the contractions elicited by 15-HPETE. In brachiocephalic arteries obtained from cholesterol-fed rabbits, 15-HPETE, 5-HT and platelets caused contractions similar to those obtained in control rabbits. The potentiating effect of 5-HT and platelets on the 15-HPETE-induced contractions was also comparable to that observed in control rabbits. Moreover, no difference was found between control platelets and platelets obtained from hypercholesterolemic rabbits. Our findings demonstrate a positive interaction between 5-HT and 15-lipoxygenase metabolites of arachidonic acid in arteries and veins. This interaction persists in atherosclerotic arteries and could indicate that this mechanism is involved in the genesis of vasospasm.
Van Diest
M J
MJ
University of Antwerp (UIA), Antwerp-Wilrijk, Belgium.
Verbeuren
T J
TJ
Herman
A G
AG
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000503:physiopathology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D012501:Saphenous Vein / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D014662:Vasoconstrictor Agents; D012701:Serotonin; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D007650:Ketanserin; D001093:Arachidonate 15-Lipoxygenase; D010646:Phentolamine