EICOSANOID SYNTHESIS IN CARDIOMYOCYTES - INFLUENCE OF HYPOXIA, REOXYGENATION, AND POLYUNSATURATED FATTY-ACIDS

The synthesis of eicosanoids was investigated in cultured rat ventricular myocytes. Under normoxia, the cardiomyocytes released 6-ketoprostaglandin F-1 alpha (6-keto-PGF(1 alpha)) and prostaglandin (PG) E(2) and smaller amounts of PGF(2 alpha) and thromboxane B-2. Hypoxia enhanced the production of PGE(2 alpha) and PGF(2 alpha), whereas the synthesis of 6-keto-PGF(1 alpha) was not affected. Conversely, posthypoxic reoxygenation greatly increased the synthesis of 6-keto-PGF(1 alpha), whereas the synthesis of PGF(2 alpha) was not affected and that of PGE(2) was reduced. The cardiomyocyte polyunsaturated fatty acid (PUFA) profile was altered by arachidonic acid or eicosapentaenoic acid and docosahexaenoic acid. Under normoxia, the eicosanoid production appeared to be roughly related to the cell phospholipid arachidonic acid content. Conversely, during posthypoxic reoxygenation, the production of eicosanoids was related to the cell phospholipid n-3 PUFA content, with the n-3-rich cells displaying a marked inhibition of the synthesis. This inhibition was mainly attributed to eicosapentaenoic acid and/or docosapentaenoic acid. Whether this inhibition occurs in vivo during postischemic reperfusion, it may contribute to the beneficial effect of n-3 PUFA on the heart.