Soluble epoxide hydrolase modulates adenosine receptor‐induced vascular response in mouse mesenteric arteries

Abstract

Soluble epoxide hydrolase (sEH) degrades epoxyeicosatrienoic acids (EETs) to less active diols (dihydroxyeicosatrienoic acids; DHETs). EETs are endothelium-derived hyperpolarizing factors (EDHFs) which play an important role in protection from ischaemic injury and have anti-inflammatory actions. Previously, we have reported upregulation of A2A adenosine receptor (AR), CYP2J2, and PPARg, and the downregulation of A1AR and PPARa in mouse aorta from sEH−/− mice with enhanced vascular relaxation. Additionally, A1AR stimulation inhibits BK channel activity involving PKCa in mouse aorta. In present study, we investigated whether over-expression of sEH in endothelium (Tie2-sEH Tr) regulates AR dependent vascular response in mouse mesenteric arteries (MAs). We performed DMT myograph muscle tension measurements and western blot (WB) in WT and Tie2-sEH Tr mice. The data show that endothelial response was comparable between Tie2-sEH Tr vs. WT mice. Phenylephrine induced contraction was significantly higher in Tie2-sEH Tr vs. WT mice. Importantly, NECA (non-selective AR agonist)-induced relaxation was significantly reduced in Tie2-sEH Tr vs. WT mice. WB analysis revealed significantly higher expression of cyp4a and upregulation of A1AR in Tie2-sEH Tr vs. WT mice. Notably, pinacidil (KATP channel opener) induced relaxation was also significantly reduced in Tie2-sEH Tr vs. WT mice. In conclusion our data suggest that over-expression of sEH reduces relaxation possibly due to upregulation of A1AR, that may show a possible interaction between sEH and ARs (HL-114559, Z01-ES025034, HL027339 & HL094447).