Erythrocyte hydrolysis of cis‐ and trans‐epoxyeicosatrienoic acids

Abstract

We have found that erythrocytes serve as a reservoir for cis- and trans-epoxyeicosatrienoic acids (EETs) that are vasoactive and antiinflammatory (JBC, 279:, 2004). Incubation of rat red blood cells (RBCs) with cis- and trans-EETs produces dihydroxyeicosatrienoic acids as analyzed by LC/MS. The hydration of trans-EETs by RBCs is 5 times faster than that of the corresponding cis-EETs. Rat erythrocytes hydrolyzed 14,15-trans-EET at ca. 1 pmol/min/109cells. The initial rates of EET hydrolysis decreased at ca. 2 fold sequentially from 14,15-, 11,12-, 8,9- to 5,6-EET for both the cis- and trans-isomers. Incubation of EETs with recombinant epoxide hydrolase yielded the same preferences. Erythrocyte hydration of cis- and trans-EETs is inhibited by the soluble epoxide hydrolase (sEH) inhibitor, 1,3-dicyclohexylurea. Preferred hydrolysis of 14,15-EETs and trans-epoxides is characteristic of sEH activities in RBCs. sEH inhibitors have vasoprotective and antihypertensive effects. As plasma trans-EET levels would increase more than cis-EETs with sEH inhibition, the role of trans-EETs in the circulation deserves attention. Supported by the Philip Morris USA Inc. and Philip Morris International (HJ) and by NIH HL-25394 (JCM).