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Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor
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 A(2A) receptor-induced enhance relaxation, but we did not see the response in CYP2J-epoxyge...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014568/ https://www.ncbi.nlm.nih.gov/pubmed/32116704 http://dx.doi.org/10.3389/fphar.2020.00027 |
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author | Agba, Stephanie Hanif, Ahmad Edin, Matthew L. Zeldin, Darryl C. Nayeem, Mohammed A. |
author_facet | Agba, Stephanie Hanif, Ahmad Edin, Matthew L. Zeldin, Darryl C. Nayeem, Mohammed A. |
author_sort | Agba, Stephanie |
collection | PubMed |
description | 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 A(2A) 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(−5)M) and Ang-II (10(−6)M). 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(−5)M (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. |
format | Online Article Text |
id | pubmed-7014568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70145682020-02-28 Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor Agba, Stephanie Hanif, Ahmad Edin, Matthew L. Zeldin, Darryl C. Nayeem, Mohammed A. Front Pharmacol Pharmacology 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 A(2A) 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(−5)M) and Ang-II (10(−6)M). 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(−5)M (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. Frontiers Media S.A. 2020-02-05 /pmc/articles/PMC7014568/ /pubmed/32116704 http://dx.doi.org/10.3389/fphar.2020.00027 Text en Copyright © 2020 Agba, Hanif, Edin, Zeldin and Nayeem http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Agba, Stephanie Hanif, Ahmad Edin, Matthew L. Zeldin, Darryl C. Nayeem, Mohammed A. Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor |
title | Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor |
title_full | Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor |
title_fullStr | Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor |
title_full_unstemmed | Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor |
title_short | Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor |
title_sort | cyp2j5-gene deletion affects on acetylcholine and adenosine-induced relaxation in mice: role of angiotensin-ii and cyp-epoxygenase inhibitor |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014568/ https://www.ncbi.nlm.nih.gov/pubmed/32116704 http://dx.doi.org/10.3389/fphar.2020.00027 |
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