Adenosine A2A receptor and vascular response: role of soluble epoxide hydrolase, adenosine A1 receptor and angiotensin-II.

Previously, we have reported that the coronary reactive hyperemic response was reduced in adenosine A_2A receptor-null (A_2AAR^−/−) mice, and it was reversed by the soluble epoxide hydrolase (sEH) inhibitor. However, it is unknown in aortic vascular response, therefore, we hypothesized that A_2AAR-gene deletion in mice (A_2AAR^−/−) affects adenosine-induced vascular response by increase in sEH and adenosine A₁ receptor (A₁AR) activities. A_2AAR^−/− mice showed an increase in sEH, A_I AR and CYP450-4A protein expression but decrease in CYP450-2C compared to C57Bl/6 mice. NECA (adenosine-analog) and CCPA (adenosine A₁ receptor-agonist)-induced dose-dependent vascular response was tested with t-AUCB (sEH-inhibitor) and angiotensin-II (Ang-II) in A_2AAR^−/− vs. C57Bl/6 mice. In A_2AAR^−/−, NECA and CCPA-induced increase in dose-dependent vasoconstriction compared to C57Bl/6 mice. However, NECA and CCPA-induced dose-dependent vascular contraction in A_2AAR^−/− was reduced by t-AUCB with NECA. Similarly, dose-dependent vascular contraction in A_2AAR^−/− was reduced by t-AUCB with CCPA. In addition, Ang-II enhanced NECA and CCPA-induced dose-dependent vascular contraction in A_2AAR^−/− with NECA. Similarly, the dose-dependent vascular contraction in A_2AAR^−/− was also enhanced by Ang-II with CCPA. Further, t-AUCB reduced Ang-II-enhanced NECA and CCPA-induced dose-dependent vascular contraction in A_2AAR^−/− mice. Our data suggest that the dose-dependent vascular contraction in A_2AAR^−/− mice depends on increase in sEH, A₁AR and CYP4A protein expression. [ABSTRACT FROM AUTHOR]