AUTHOR=Agba Stephanie , Hanif Ahmad , Edin Matthew L. , Zeldin Darryl C. , Nayeem Mohammed A. 

TITLE=Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00027

DOI=10.3389/fphar.2020.00027

ISSN=1663-9812

ABSTRACT=<p>Previously, we showed vascular endothelial overexpression of human-CYP2J2 enhances coronary reactive hyperemia in Tie2-CYP2J2 Tr mice, and eNOS<sup>−/−</sup> mice had overexpression of CYP2J-epoxygenase with adenosine A<sub>2A</sub> receptor-induced enhance relaxation, but we did not see the response in CYP2J-epoxygenase knockout mice. Therefore, we hypothesized that <italic>Cyp2j5</italic>-gene deletion affects acetylcholine- and 5'-N-ethylcarboxamidoadenosine (NECA) (adenosine)-induced relaxation and their response is partially inhibited by angiotensin-II (Ang-II) in mice. Acetylcholine (Ach)-induced response was tested with <italic>N</italic>-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH, CYP-epoxygenase inhibitor; 10<sup>−5</sup>M) and Ang-II (10<sup>−6</sup>M). In <italic>Cyp2j5<sup>−/−</sup></italic> mice, ACh-induced relaxation was different from C57Bl/6 mice, at 10<sup>−5</sup> M (76.1 ± 3.3 <italic>vs.</italic> 58.3 ± 5.2, <italic>P</italic> &lt; 0.05). However, ACh-induced relaxation was not blocked by MS-PPOH in <italic>Cyp2j5<sup>−/−</sup></italic>: 58.5 ± 5.0%, <italic>P</italic> &gt; 0.05, but blocked in C57Bl/6: 52.3 ± 7.5%, <italic>P</italic> &lt; 0.05, and Ang-II reduces ACh-induced relaxation in both <italic>Cyp2j5<sup>−/−</sup></italic> and C57Bl/6 mice (38.8 ± 3.9% and 45.9 ± 7.8, <italic>P &lt;</italic>0.05). In addition, NECA-induced response was tested with Ang-II. In <italic>Cyp2j5<sup>−/−</sup></italic> mice, NECA-induced response was not different from C57Bl/6 mice at 10<sup>−5</sup>M (23.1 ± 2.1 <italic>vs.</italic> 21.1 ± 3.8, <italic>P</italic> &gt; 0.05). However, NECA-induced response was reduced by Ang-II in both <italic>Cyp2j5<sup>−/−</sup></italic> and C57Bl/6 mice (−10.8 ± 2.3% and 3.2 ± 2.7, <italic>P &lt;</italic> 0.05). Data suggest that ACh-induced relaxation in <italic>Cyp2j5<sup>−/−</sup></italic> mice depends on nitric oxide (NO) but not CYP-epoxygenases, and the NECA-induced different response in male <italic>vs.</italic> female <italic>Cyp2j5<sup>−/−</sup></italic> mice when Ang-II treated.</p>