Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 83-95 |
| Number of pages | 13 |
| Journal | Prostaglandins and Other Lipid Mediators |
| Volume | 131 |
| DOIs | |
| State | Published - Jul 1 2017 |
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Keywords
- Adenosine A receptor
- Coronary reactive hyperemia
- Heart perfusate oxylipins
- Plasma oxylipins
- Soluble epoxide hydrolase
- ω-hydroxylases
ASJC Scopus subject areas
- Physiology
- Biochemistry
- Pharmacology
- Cell Biology
Cite this
Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB) : Role of adenosine A2A receptor and plasma oxylipins. / Hanif, Ahmad; Edin, Matthew L.; Zeldin, Darryl C.; Morisseau, Christophe; Falck, J R; Ledent, Catherine; Tilley, Stephen L.; Nayeem, Mohammed A.
In: Prostaglandins and Other Lipid Mediators, Vol. 131, 01.07.2017, p. 83-95.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduced coronary reactive hyperemia in mice was reversed by the soluble epoxide hydrolase inhibitor (t-AUCB)
T2 - Role of adenosine A2A receptor and plasma oxylipins
AU - Hanif, Ahmad
AU - Edin, Matthew L.
AU - Zeldin, Darryl C.
AU - Morisseau, Christophe
AU - Falck, J R
AU - Ledent, Catherine
AU - Tilley, Stephen L.
AU - Nayeem, Mohammed A.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - Adenosine A receptor
KW - Coronary reactive hyperemia
KW - Heart perfusate oxylipins
KW - Plasma oxylipins
KW - Soluble epoxide hydrolase
KW - ω-hydroxylases
UR - http://www.scopus.com/inward/record.url?scp=85029518121&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029518121&partnerID=8YFLogxK
U2 - 10.1016/j.prostaglandins.2017.09.001
DO - 10.1016/j.prostaglandins.2017.09.001
M3 - Article
C2 - 28890385
AN - SCOPUS:85029518121
VL - 131
SP - 83
EP - 95
JO - Prostaglandins and Other Lipid Mediators
JF - Prostaglandins and Other Lipid Mediators
SN - 1098-8823
ER -