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

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