Renal microvascular activity of cis- and trans-epoxyeicosatrienoic acids

Anabel Doumad, Houli Jiang, John Quilley, John McGiff, Mairead Carroll. New York Medical College, Valhalla, New York, United States.

Epoxyeicosatrienoic acids (EETs) are vasodepressor, natriuretic and anti-inflammatory lipid mediators (Spector et al., 2007). EETs are stored as both cis- and trans-isomers in plasma phospholipids and red blood cell (RBC) membranes (Jiang et al., 2005). In RBCs, trans- EETs are preferentially hydrolyzed, over cis-EETs, by soluble epoxide hydrolase (sEH). As RBCs provide an abundant pool of EETs, we compared the renal vasoactivity (10-12 M to 10-7 M) of the cis- and trans- EET regioisomers (8, 9-, 11, 12- and 14, 15-EETs). Microdissected arcuate arteries (∼110 μm internal diameter; i.d.) of anaesthetized, male Sprague-Dawley rats (225-250g) were pressurized to 80 mmHg and superfused with Krebs’ solution containing indomethacin (10 μM) and L-NAME (200 μM). Vessels were preconstricted with phenylephrine (10-7 M) and i.d. measured with a video dimension analyzer. Of the cis-EETs, the 11, 12-EET was the most potent vasodilator (ED50 5 x 10-9 M), with a maximum response of -44 ± 9 μm. In contrast, the trans-EETs displayed equipotent, concentration-dependent vasodilation (ED50 5 x 10-10 M). The maximal responses of 8, 9-trans-EET (-43 ± 10 μm) and 14, 15-trans-EET (-45 ± 7 μm) were significantly greater than those of their respective cis-isomers (-19 ± 6 μm for 8, 9-EET and -10 ± 4 μm for 14, 15-EET), whereas, the maximum response of 11, 12-trans-EET (-63 ± 11 μm) was similar to that of 11, 12-cis-EET. The greater vasodilator potency of trans-EETs vs. cis-EETs may contribute to the antihypertensive effects of sEH inhibitors.

Spector et al., (2007) Am J Physiol Cell Physiol. 292:C996-1012.
Jiang et al., (2005) Prostaglandins Other Lipid Mediat. 75:65-78.