20-hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries

Recently we have demonstrated that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) constricts rat aortic rings and that this effect is cyclooxygenase- and endothelium-dependent. Incubation of 20-HETE with ram seminal vesicles, a rich source of cyclooxygenase, led to the identification of vasoconstrictor metabolites, the 20-hydroxy-endoperoxides. In the present study, we demonstrated differences in the potency of 20-HETE to constrict several arteries. In all blood vessels tested, the 20-HETE contractile effect was cyclooxygenase- and endothelium-dependent. Differences in contractile potency of 20-HETE varied according to the blood vessels; potency being higher in more muscular arteries than elastic ones. Furthermore, 20-HETE was more potent in eliciting vasoconstriction than its precursor, arachidonic acid. We also provide evidence for the generation of 20-hydroxy-endoperoxides from 20-HETE by the endothelial cyclooxygenase. 20-HETE is a major arachidonate metabolite formed by the cytochrome P450 monooxygenases in rat, human and rabbit kidneys. In addition, blood cells such as leukocytes have the ability to produce 20-HETE, suggesting its presence in the circulation. Furthermore, 20-HETE has been shown to inhibit platelet aggregation. Thus, the ability of 20-HETE to modulate vascular tone and platelet function implicates a role for this compound in the regulation of hemostasis.