When bovine pulmonary artery endothelial cells are cultured in a medium supplemented with linoleic acid, their capacity to produce prostacyclln (PGI 2 ) is reduced by about 60%. This reduction occurs when PGI 2 formation Is stimulated by the addition of either the calcium lonophore A23187 or arachidonic acid. In addition, supplementation with linoleic acid reduced the production of prostaglandin E 2 and F 2n from 1-14 Carachidonic acid by more than 50%. The capacity of cultured bovine pulmonary vein and aortic endothelial cells to convert extracellular arachidonic acid Into PGI 2 also was reduced by about 50% when the growth medium was supplemented with linoleic acid. Although bovine pulmonary artery endothelial cells Incorporated large amounts of 1-14 C-linolelc acid into cellular phospholiplds and triglycerldes, a maximum of only 2.3% of the radioactivity was converted to arachidonic acid In 24 hours. The most prevalent radioactive metabolite was elcosadlenoic acid, the elongation product of linoleic acid. As compared with linoleic acid, the bovine endothelial cells Incorporated 30% more 1-14 C-arachldonlc acid Into phospholiplds and 60% more Into triglycerldes. When the growth medium was supplemented with linoleic acid, the percentage of this fatty acid In cellular liplds Increased 3-to 4.5-fold and eicosadlenoic acid accumulated, accounting for up to 9% of the cellular fatty acids. This Increase was accompanied by a 30% to 45% reduction in arachidonic acid. These findings, together with our previous results with human umbilical vein endothellum, suggest that an inability to convert large amounts of linoleic to arachidonic acid and a suppresslve effect of linoleic acid enrichment on prostaglandin production may be general properties of endothelial cells. 'The notation n-6 refers to the fact that the first double bond is 6 carbon atoms removed from the methyl terminus in this class of polyunsaturated fatty acids. Linoleic and arachidonic acids are members of the n-6 class.human umbilical vein endothelial cells revealed several unexpected results regarding linoleic acid metabolism and its effect on PGI 2 production. These cultures were found to convert only very small amounts of linoleic acid to arachidonic acid. 4 Furthermore, supplementation with linoleic acid produced a reduction in the arachidonic acid content of the cellular phospholipids and a decreased capacity of the cells to release PGI 2 .58 Similar effects of linoleic acid supplementation on prostaglandin production have not been observed in Madin-Darby canine kidney (MDCK) or 3T3 cells, both of which release predominantly prostaglandin E 2 (PGE 2 ). These cells accumulate increased amounts of arachidonic acid in phospholipids when they are enriched with linoleic acid, and PGE 2 production is enhanced.78 MDCK cells are derived from dog kidney tubular epithelium, and 3T3 cells are from a mouse embryo. Although these cells probably have different properties than cells of vascular origin, the fact that the findings were so different made it of interest ...