Cytochrome P450 metabolites of arachidonic acid: rapid incorporation and hydration of 14,15-epoxyeicosatrienoic acid in arterial smooth muscle cells

Arachidonic acid is converted to epoxyeicosatrienoic acids (EETs) by cytochrome P450 monooxygenases. EETs produce arterial vasodilatation, and recent evidence suggests that they are endothelium-derived hyperpolarizing factors. In porcine coronary arteries contracted with a thromboxane mimetic agent, we find that relaxation is rapidly initiated by exposure to 14,15-EET. The relaxation slowly increases in magnitude, resulting in a response which is sustained for more than 10 min. Cultured porcine aortic smooth muscle cells rapidly take up [ 3H]14,15-EET. After 3 min, radioactivity is present in neutral lipids, phosphatidylcholine, and phosphatidylinositol. The cells also convert 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), and some DHET is detected in the medium after only 1 min of incubation. Like 14,15-EET, 14,15-DHET produces relaxation of the contracted coronary artery rings. These findings suggest that the incorporation into phospholipids and conversion to 14,15-DHET can occur at a rate that is fast enough to modulate the vasorelaxation produced by 14,15-EET.