| First Author | Hanif A | Year | 2017 |
| Journal | Prostaglandins Other Lipid Mediat | Volume | 131 |
| Pages | 83-95 | PubMed ID | 28890385 |
| Mgi Jnum | J:302771 | Mgi Id | MGI:6510197 |
| Doi | 10.1016/j.prostaglandins.2017.09.001 | Citation | Hanif A, et al. (2017) Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB): Role of adenosine A2A receptor and plasma oxylipins. Prostaglandins Other Lipid Mediat 131:83-95 |
| abstractText | 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 omega-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 omega-terminal HETEs, decreased epoxyoctadecaenoic/dihydroxyoctadecaenoic acids (EpOMEs/DiHOMEs) ratios, increased 9-hydroxyoctadecadienoic acid, and increased prostanoids. Inhibition of either sEH or omega-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 omega-hydroxylases reversed the reduction in CRH. |
