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

Abstract

Previously, we showed vascular endothelial overexpression of human-CYP2J2 enhances coronary reactive hyperemia in Tie2-CYP2J2 Tr mice, and eNOS-/- mice had overexpression of CYP2J-epoxygenase with adenosine A2A receptor-induced enhance relaxation, but we did not see the response in CYP2J-epoxygenase knockout mice. Therefore, we hypothesized that Cyp2j5-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 N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH, CYP-epoxygenase inhibitor; 10-5M) and Ang-II (10-6M). In Cyp2j5-/- mice, ACh-induced relaxation was different from C57Bl/6 mice, at 10-5 M (76.1 ± 3.3 vs. 58.3 ± 5.2, P < 0.05). However, ACh-induced relaxation was not blocked by MS-PPOH in Cyp2j5-/- : 58.5 ± 5.0%, P > 0.05, but blocked in C57Bl/6: 52.3 ± 7.5%, P < 0.05, and Ang-II reduces ACh-induced relaxation in both Cyp2j5-/- and C57Bl/6 mice (38.8 ± 3.9% and 45.9 ± 7.8, P <0.05). In addition, NECA-induced response was tested with Ang-II. In Cyp2j5-/- mice, NECA-induced response was not different from C57Bl/6 mice at 10-5M (23.1 ± 2.1 vs. 21.1 ± 3.8, P > 0.05). However, NECA-induced response was reduced by Ang-II in both Cyp2j5-/- and C57Bl/6 mice (-10.8 ± 2.3% and 3.2 ± 2.7, P < 0.05). Data suggest that ACh-induced relaxation in Cyp2j5-/- mice depends on nitric oxide (NO) but not CYP-epoxygenases, and the NECA-induced different response in male vs. female Cyp2j5-/- mice when Ang-II treated.

• Authors: Stephanie Agba, Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Mohammed A Nayeem
• Journal: Frontiers in pharmacology (Front Pharmacol) Vol. 11 Pg. 27 ( 2020) ISSN: 1663-9812 [Print] Switzerland
• PMID: 32116704 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Agba, Hanif, Edin, Zeldin and Nayeem.