Ephx2 -gene deletion affects acetylcholine-induced relaxation in angiotensin-II infused mice: role of nitric oxide and CYP-epoxygenases

摘要: Previously, we showed that adenosine A2A receptor induces relaxation independent of NO in soluble epoxide hydrolase-null mice (Nayeem et al. Am J Physiol Regul Integr Comp 304:R23–R32, 2013). Currently, hypothesize Ephx2-gene deletion affects acetylcholine (Ach)-induced which is A2AAR but dependent on and CYP-epoxygenases. Ephx2−/− aortas a lack sEH (97.1%, P   0.05). Ach-induced response was tested with nitro-l-arginine methyl ester (l-NAME) NO-inhibitor; 10−4 M), N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH) (CYP-epoxygenase inhibitor; 10−5 M), 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an epoxyeicosatrienoic acid-antagonist; SCH-58261 (A2AAR-antagonist; 10−6 M), angiotensin-II (Ang-II, 10−6 M). In mice, not different from C57Bl/6 except at 10−5 M (92.75 ± 2.41 vs. 76.12 ± 3.34,  0.05) non-treated (P > 0.05). Interestingly, Ang-II attenuates less Ehx2−/− (58.80 ± 7.81% 45.92 ± 7.76, P < 0.05). Our data suggest depends CYP-epoxygenases AR, Ang-II-infused mice.