Endothelium-dependent hyperpolarizations and relaxation of vascular smooth muscle induced by acetylcholine and bradykinin are mediated by endothelium-derived hyperpolarizing factors (EDHFs). Arachidonic acid is metabolizedby cytochrome-P450 (CYP450) to four regioisomeric epoxyeicosatrienoic acids (EETs) that function as EDHFs.  5,6-, 8,9-, 11,12- and 14,15-EET are equipotent in relaxing bovine coronary arteries (BCAs). The miconazole analog, WX-III-287-19 was synthesized and compared to EETsin causing relaxations of BCAs. EETs vascular relaxation responses were recorded using isometric tension recording.  BCA metabolism of 20-H-11,12-EE8ZE was analyzed by mass spectrometry. In U-46619-preconstricted arterial rings, WX-III-287-19 caused concentration-dependent relaxation with maximal relaxation ranging from 95-100%; however, relaxations by 5,6-8,9-11,12 and 14,15 EETs were less than WX-III-287-19. Preincubation of arteries with the EET antagonist,14,15-EEZE (10^-5 M) did not inhibit relaxation to WX-III-287-19, but inhibited relaxation to 5,6-8,9-11,12 and 14,15 EETs. Preincubation with the iberiotoxin (10^-5 M) only partially inhibited the relaxation induced by WX-III-287-19 whereas high K⁺ (60 mM) significantly inhibited relaxation to WX-III-287-19. In whole cell-attached patches of isolated bovine coronary arterial smooth muscle cells, WX-III-287-19 did not alter activation of large-conductance, calcium-activated K⁺ channels.In U-46619-preconstricted rabbit aortic rings, WX-III-287-19 caused relaxation; however, relaxations were not observed in arteries preconstricted with either high K⁺ (60 mM) and pheynylephrine (10^-5 M). These results indicate that WX-III-287-19 is a potent coronary vasorelaxant and may act as a thromboxane receptor antagonist.