摘要 : Previously, we have reported that the coronary reactive hyperemic response was reduced in adenosine A(2A) receptor-null (A(2A)AR(-/-)) mice, and it was reversed by the soluble epoxide hydrolase (sEH) inhibitor. However, it is unkn... 展开 Previously, we have reported that the coronary reactive hyperemic response was reduced in adenosine A(2A) receptor-null (A(2A)AR(-/-)) 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(2A)AR-gene deletion in mice (A(2A)AR(-/-)) affects adenosine-induced vascular response by increase in sEH and adenosine A(1) receptor (A(1)AR) activities. A(2A)AR(-/-) 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 A(1) receptor-agonist)-induced dose-dependent vascular response was tested with t-AUCB (sEH-inhibitor) and angiotensin-II (Ang-II) in A(2A)AR(-/-) vs. C57Bl/6 mice. In A(2A)AR(-/-), 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(2A)AR(-/-) was reduced by t-AUCB with NECA. Similarly, dose-dependent vascular contraction in A(2A)AR(-/-) was reduced by t-AUCB with CCPA. In addition, Ang-II enhanced NECA and CCPA-induced dose-dependent vascular contraction in A(2A)AR(-/-) with NECA. Similarly, the dose-dependent vascular contraction in A(2A)AR(-/-) 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(2A)AR(-/-) mice. Our data suggest that the dose-dependent vascular contraction in A(2A)AR(-/-) mice depends on increase in sEH, A(1)AR and CYP4A protein expression. 收起