TY - JOUR
T1 - 20-Hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries
AU - Escalante, Bruno
AU - Omata, Ken
AU - Sessa, William
AU - Lee, Sang Gyeong
AU - Falck, J R
AU - Schwartzman, Michal Laniado
N1 - Funding Information:
This study was supported in part by the National Institutes of Health Grants HL 34300 and GM 31278 and by the G. Harold and
PY - 1993/4/22
Y1 - 1993/4/22
N2 - 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, arachiddonic 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.
AB - 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, arachiddonic 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.
KW - 20-HETE (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
KW - Arachidonic acid
KW - Cytochrome P450
KW - Endothelium-dependent vasoconstrictor
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U2 - 10.1016/0014-2999(93)90812-V
DO - 10.1016/0014-2999(93)90812-V
M3 - Article
C2 - 8519270
AN - SCOPUS:0027229302
SN - 0014-2999
VL - 235
SP - 1
EP - 7
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -