Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor ( t -AUCB): Role of adenosine A 2A receptor and plasma oxylipins
Copyright policy )Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor ( t -AUCB): Role of adenosine A 2A receptor and plasma oxylipins
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-hydroxylases reversed the reduced CRH in A2AAR-/- mice. In WT and sEH-/- mice, blocking A2AAR decreased CRH. These data demonstrate that A2AAR-deletion was associated with changes in oxylipin profiles, which may contribute to the attenuated CRH. Also, inhibition of sEH and ω-hydroxylases reversed the reduction in CRH.
- University of North Carolina at Chapel Hill United States
- University of California, Davis United States
- National Institute of Health Pakistan
- University of California, San Francisco United States
- Université Libre de Bruxelles Belgium
Biochemistry & Molecular Biology, Receptor, Adenosine A2A, Biochimie, Medical Physiology, Hyperemia, Adenosine A2A receptor, Pharmacologie, Medical Biochemistry and Metabolomics, Cardiovascular, Inbred C57BL, Benzoates, Adenosine A2A, Mice, Physiologie générale, Coronary reactive hyperemia, Medical biochemistry and metabolomics, Animals, Urea, Oxylipins, Plasma oxylipins, Enzyme Inhibitors, Epoxide Hydrolases, Biomedical and Clinical Sciences, Coronary Vessels, Heart perfusate oxylipins, Adenosine A2 Receptor Antagonists, Mice, Inbred C57BL, Heart Disease, Soluble epoxide hydrolase, Solubility, Biochemistry and cell biology, Adenosine A(2A) receptor, ω-hydroxylases, Biologie cellulaire, omega-hydroxylases, Receptor
Biochemistry & Molecular Biology, Receptor, Adenosine A2A, Biochimie, Medical Physiology, Hyperemia, Adenosine A2A receptor, Pharmacologie, Medical Biochemistry and Metabolomics, Cardiovascular, Inbred C57BL, Benzoates, Adenosine A2A, Mice, Physiologie générale, Coronary reactive hyperemia, Medical biochemistry and metabolomics, Animals, Urea, Oxylipins, Plasma oxylipins, Enzyme Inhibitors, Epoxide Hydrolases, Biomedical and Clinical Sciences, Coronary Vessels, Heart perfusate oxylipins, Adenosine A2 Receptor Antagonists, Mice, Inbred C57BL, Heart Disease, Soluble epoxide hydrolase, Solubility, Biochemistry and cell biology, Adenosine A(2A) receptor, ω-hydroxylases, Biologie cellulaire, omega-hydroxylases, Receptor
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