EFFECTS OF LINOLEIC AND OLEIC-ACID ANILIDES ON PROSTACYCLIN SYNTHESISAND FIBRINOLYTIC PROFILE OF HUMAN ENDOTHELIAL-CELLS IN CULTURE - RELEVANCE TO THE TOXIC OIL SYNDROME

We evaluated the effects of fatty-acid anilides (FAA) on prostacyclin (PGI2) synthesis and on the fibrinolytic properties of human umbilical vein endothelial cells. Preincubation of endothelial cells with oleic - and linoleic-anilides (OAA and LAA, respectively) resulted in a time - and concentration-dependent inhibition of ionophore A23187- and thro mbin-induced PGI2 synthesis. However, no significant effects of FAA on arachidonic acid-induced PGI2 synthesis were found, except with 1000 muM LAA which inhibited cyclooxygenase activity after 24 h. In general terms, OAA showed similar inhibitory effects on PGI2 production as di d LAA, but with a shifted time course, since the production of PGI2 at 24 h for OAA was similar to that observed for LAA at 2 h. The release of labeled arachidonic acid from cell membranes was significantly red uced (75-85%), after 24 h, with both FAA. The effect of 100 muM LAA on thrombin-induced PGI2 Production was rapid (within 15 min) and irreve rsible after 60 min. The recovery of PGI2 synthesis after LAA treatmen t was blocked by cycloheximide, suggesting a decrease of phospholipase (s) activity or cessation of enzyme synthesis. Moreover, this reduced PGI2 synthesis was not associated with [H-3]adenine release. Our data indicate that FAA induce a significant impairment of stimulated PGI2 s ynthesis and arachidonic acid release in endothelial cells, acting pri marily as inhibitors of phospholipase(s) rather than of cyclooxygenase . Finally, both LAA and OAA induce an anti-fibrinolytic activity in th ese cells where major changes are observed in the plasminogen activato r inhibitor and the urine-type plasminogen activator.