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Cytochrome P‐450 epoxygenase 2J2 modulates adenosine receptor‐mediated vascular response in mouse mesenteric arteries
Author(s) -
Yadav Vishal,
Zeldin Darryl,
Mustafa S Jamal,
Xie Sherry,
Nayeem Mohammed
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.627.11
Subject(s) - epoxygenase , chemistry , endocrinology , medicine , epoxide hydrolase 2 , mesenteric arteries , myograph , agonist , downregulation and upregulation , adenosine , iberiotoxin , phenylephrine , arachidonic acid , receptor , vasodilation , biochemistry , biology , artery , enzyme , gene , blood pressure
Cytochrome P‐450 epoxygenases including CYP2J2 are expressed in vascular endothelial cells that generate epoxyeicosatrienoic acids (EETs) through epoxidation of arachidonic acid. EETs are endothelium‐derived hyperpolarizing factors which are protective in nature and are degraded by soluble epoxide hydrolase (sEH). In aorta from sEH −/− mice, we reported upregulation of A 2A adenosine receptor (AR), CYP2J2, and PPARg, and the downregulation of A 1 AR and PPARa with enhanced vascular relaxation. In this study, we explored whether over‐expression of CYP2J2 in endothelium (Tie2‐CYP2J2 Tr) regulates AR dependent vascular responses in mouse mesenteric arteries (MAs). We performed DMT myograph experiments in WT and Tie2‐CYP2J2 Tr mice. Our findings revealed that acetylcholine‐dependent response was unchanged. Phenylephrine and KCl induced contractions were significantly higher in Tie2‐CYP2J2 Tr vs. WT mice (p<0.05). Importantly, CCPA (selective A 1 AR agonist)‐induced contractions were significantly reduced in Tie2‐CYP2J2 Tr vs. WT mice (p<0.05). NECA (non‐selective AR agonist)‐induced relaxation was similar Tie2‐sEH Tr vs. WT mice. Especially, pinacidil (K ATP channel opener) induced relaxation was also significantly enhanced in Tie2‐CYP2J2 Tr vs. WT mice. Our data suggest that over‐expression of CYP2J2 enhances vascular relaxation possibly due to the combination of reduction in A 1 AR‐dependent contraction and enhancement of relaxation through K ATP channel, indicating a possible interaction among CYP2J2, ARs and K ATP channels ( HL‐114559, Z01‐ES025034 , HL027339 & HL094447) .