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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 |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
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 |
Sumario: | 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. |
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