DOCOSAPENTAENOIC ACID (22 5,N-3) - METABOLISM END EFFECT ON PROSTACYCLIN PRODUCTION IN ENDOTHELIAL-CELLS/

Eicosapentaenoic acid (EPA, 20:5,n-3) and docosahexaenoic acid (DHA, 2 2:6,n-3), the two main fatty acids of fish oil, have been shown to inh ibit prostacyclin production and to be actively interconverted, leadin g to the accumulation of docosapentaenoic acid (DPA, 22:5,n-3) in endo thelial cell phospholipids. We have investigated the effect of supplem enting endothelial cells with DPA on their capacity to produce prostac yclin. We found that endothelial cells incubated for 22 h with 25 mu M DPA bound to albumin (fatty acid/albumin ratio of 1.3) produced two-f old less prostacyclin compared to control cells when stimulated with e ndogenous arachidonic acid-mobilizing agents such as bradykinin and ca lcium ionophore A23187. Since the formation of prostacyclin from 0.1-1 5 mu M exogenous arachidonic acid was also reduced, it is suggested th at prostacyclin inhibition observed in DPA-treated cells might not pro ceed from a reduction of arachidonic acid availability only. Such an i nhibition was already observed after 1 h incubation of the cells with DPA, and with 2-20 times lower DPA concentrations. The inhibition migh t depend on EPA which was formed by retroconversion of DPA.