Affordable Access

deepdyve-link
Publisher Website

Possible inhibitory function of endogenous 15-hydroperoxyeicosatetraenoic acid on prostacyclin formation in bovine aortic endothelial cells

Authors
  • Mayer, Bernd
  • Moser, Robert
  • Gleispach, Helmut
  • Kukovetz, Walter R.
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
Publisher
Elsevier
Publication Date
Jan 01, 1986
Volume
875
Issue
3
Pages
641–653
Identifiers
DOI: 10.1016/0005-2760(86)90088-3
Source
Elsevier
Keywords
License
Unknown

Abstract

Arachidonic acid is metabolized via the cyclooxygenase pathway to several potent compounds that regulate important physiological functions in the cardiovascular system. The proaggregatory and vasoconstrictive thromboxane A 2 produced by platelets is opposed in vivo by the antiaggregatory and vasodilating activity of prostacyclin (prostaglandin I 2) synthesized by blood vessels. Furthermore, arachidonic acid is metabolized by lipoxygenase enzymes to different isomeric hydroxyeicosatetraenoic acids (HETE's). This metabolic pathway of arachidonic acid was studied in detail in endothelial cells obtained from bovine aortae. It was found that this tissue produced 6-ketoprostaglandin F 1α as a major cyclooxygenase metabolite of arachidonic acid, whereas prostaglandins F 2α and E 2 were synthesized only in small amounts. The monohydroxy fatty acids formed were identified as 15-HETE, 5-HETE, 11-HETE and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT). The latter two compounds were produced by cyclooxygenase activity. Nordihydroguaiaretic acid (NDGA), a rather selective lipoxygenase inhibitor and antioxidant blocked the synthesis of 15- and 5-HETE. It also strongly stimulated the cyclooxygenase pathway, and particularly the formation of prostacyclin. This could indicate that NDGA might exert its effect on prostacyclin levels by preventing the synthesis of 15-hydroperoxyeicosatetraenoic acid (15-HPETE), a potent inhibitor of prostacyclin synthetase. 15-HPETE could therefore act as an endogenous inhibitor of prostacyclin production in the vessel wall.

Report this publication

Statistics

Seen <100 times