Eicosapentaenoic acid reduces thrombin-evoked release of endothelin-1 in cultured bovine endothelial cells.
Endothelial cells were isolated from bovine thoracic aorta and cultured. Bovine aortic endothelial cells (BAEC) were incubated with radiolabeled arachidonic acid (3H-AA) or eicosapentaenoic acid (14C-EPA) (1 microM) for 3 hr. Both fatty acids were predominantly incorporated into phosphatidylcholine (57 +/- 2% and 62 +/- 2% respectively) and slightly into phosphatidylethanolamine (11 +/- 0.5% and 12 +/- 0.6% respectively). phosphatidylinositol (26 +/- 1.5% and 10 +/- 0.5% respectively) and neutral lipids (6 +/- 0.5% and 15 +/- 1% respectively). After BAEC incubation with 3H-AA for 24 hr with or without EPA (1 microM), the release of radioactive metabolites of AA induced by thrombin (5.5 U/ml) was strongly reduced by the preliminary treatment with EPA (72 +/- 5%). After BAEC incubation with AA, EPA or vehicle (control), endothelin-1 levels were measured by RIA in the culture medium and we observed that: 1) the basal production of endothelin-1 was not modified after either AA or EPA treatment, 2) the thrombin-evoked release of endothelin-1 was significantly reduced by EPA (5.8 +/- 0.82 and 3.8 +/- 0.50 pg/microg proteins in control and EPA-treated cells, respectively); 3) by contrast, AA had no significant effect on the thrombin-evoked release of endothelin-1. In conclusion, EPA reduces strongly the endothelin-1 release but AA is ineffective. This reduction of endothelin-1 release may account partly for some of the vascular effects of EPA.
Jamin
S P
SP
Groupe Endothélium & Physiologie de la Paroi Vasculaire, Laboratoire de Physiologie, Faculté de Pharmacie, Rennes, France.
Crabos
M
M
Catheline
M
M
Martin-Chouly
C
C
Legrand
A B
AB
Saïag
B
B
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D019332:Endothelin-1; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D013917:Thrombin