Vasoactivity of 20-hydroxyeicosatetraenoic acid is dependent on metabolism by cyclooxygenase.
We recently demonstrated that cortical microsomes from spontaneously hypertensive rats metabolize arachidonic acid via cytochrome P450 to omega- and omega-1 hydroxylated compounds, 19- and 20-hydroxyeicosatetraenoic acids (HETE). The vascular activities of 20-HETE and the two isomers of 19-HETE were examined in rat aortic rings. The HETEs produced concentration-dependent contractions of the aortic rings. The contraction elicited by 20-HETE was abolished partially by removal of endothelium and was inhibited completely by treatment with indomethacin and reversed to a relaxation response by treatment with the endoperoxide and thromboxane receptor antagonist SQ 29548. These data suggest that the vascular effects of 20-HETE depend on subsequent metabolism by cyclooxygenase.
Escalante
B
B
Department of Pharmacology, New York Medical College, Valhalla.
Sessa
W C
WC
Falck
J R
JR
Yadagiri
P
P
Schwartzman
M L
ML
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D006893:Hydroxyeicosatetraenoic Acids; D013928:Thromboxane A2; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin