EPOXYEICOSATRIENOIC ACID METABOLISM IN ARTERIAL SMOOTH-MUSCLE CELLS

Epoxyeicosatrienoic acids (EETs) are eicosanoids synthesized from arac hidonic acid by the cytochrome P450 epoxygenase pathway. The present s tudies demonstrate that 8,9-, 11,12-, and 14,15-EET are rapidly taken up by porcine aortic smooth muscle cells. About half of the uptake is incorporated into phospholipids, and saponification indicates that mos t of this remains in the form of EET. The EETs also are converted to t he corresponding dihydroxyeicosatrienoic acids (DHETs) and during prol onged incubations, additional metabolites that do nor retain the EET c arboxyl group are formed. Most of these products are released into the medium. However, some DHET and metabolites less polar than EET are in corporated into the phospholipids, and a small amount of unesterified EET is also present in the cells. The incorporation of 14,15-EET and i ts conversion to DHET did not approach saturation until the concentrat ion exceeded 10-20 mu M, indicating that vascular smooth muscle has a large capacity to utilize this EET. These findings suggest that certai n vasoactive effects of EETs may be due to their incorporation by smoo th muscle cells. Furthermore, through conversion to DHET and other oxi dized metabolites, smooch muscle apparently has the capacity to inacti vate EETs that are either formed in or penetrate into the vascular wal l.