Vasoactivity of Arachidonic Acid Epoxides

Arachidonic acid (AA) can be metabolized to epoxides and their corresponding diols via the cytochrome P450 epoxygenase pathway. We have compared the vascular activity of four synthetically prepared epoxyeicosatrienoic acids, i.e. 5,6-, 8,9-, 11,12- and 14,15-EET (2-20 microM) on the isolated perfused rat tail artery. The 5,6-EET was equipotent with acetylcholine in dose dependently reducing vascular resistance (ED50 = 3.4 +/- 0.5 microM). The 8,9-, 11,12- and 14,15-EETs of AA did not affect vascular resistance; neither did the 5,6-DHET and delta-lactone, hydrolysis products of 5,6-epoxide. We suggest that the 5,6-epoxide, in contrast to other cytochrome P450-derived products, contributes to the regulation of regional vascular tone.