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.
Department of Pharmacology, New York Medical College, Valhalla 10595.
B
B
Escalante
K
K
Omata
W
W
Sessa
S G
SG
Lee
J R
JR
Falck
M L
ML
Schwartzman
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D006893:Hydroxyeicosatetraenoic Acids; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D011451:Prostaglandin-Endoperoxide Synthases