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