Reduced Coronary Reactive Hyperemia in Mice was Reversed by the Soluble Epoxide Hydrolase Inhibitor (t-AUCB): Role of Adenosine A2A Receptor and Plasma Oxylipins

Publication date: Available online 7 September 2017 Source:Prostaglandins & Other Lipid Mediators Author(s): Ahmad Hanif, Matthew L. Edin, Darryl C. Zeldin, Christophe Morisseau, John R. Falck, Catherine Ledent, Stephen L. Tilley, Mohammed A. Nayeem Coronary reactive hyperemia (CRH) protects the heart against ischemia. Adenosine A2AAR–deficient (A2AAR−/−) mice have increased expression of soluble epoxide hydrolase (sEH); the enzyme responsible for breaking down the cardioprotective epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). sEH–inhibition enhances CRH, increases EETs, and modulates oxylipin profiles. We investigated the changes of oxylipins and their impact on CRH in A2AAR−/− and wild type (WT) mice. We hypothesized that the attenuated CRH in A2AAR−/− mice is mediated by changes in oxylipin profiles, and that it can be reversed by either sEH or ω-hydroxylases–inhibition. Compared to WT mice, A2AAR−/− mice had attenuated CRH and changed oxylipin profiles, which were consistent between plasma and heart perfusate samples, including decreased EET/DHET ratios, and increased hydroxyeicosatetraenoic acids (HETEs). Plasma oxylipns in A2AAR−/− mice indicated an increased proinflammatory state including increased ω-terminal HETEs, decreased epoxyoctadecaenoic/dihydroxyoctadecaenoic acids (EpOMEs/DiHOMEs) ratios, increased 9-hydroxyoctadecadienoic acid, and increased prostanoids. Inhibition of either sEH or ω...

Source: Prostaglandins and Other Lipid Mediators - September 8, 2017 Category: Lipidology Source Type: research