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

par Hanif, Ahmad;Agba, Stephanie S.O.;Ledent, Catherine ;Tilley, Stephen S.L.;Morisseau, Christophe;Nayeem, Mohammed M.A.
Référence Molecular and cellular biochemistry
Publication Publié, 2021-07-01

Article révisé par les pairs

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Résumé :

Previously, we have reported that the coronary reactive hyperemic response was reduced in adenosine A2A receptor-null (A2AAR−/−) mice, and it was reversed by the soluble epoxide hydrolase (sEH) inhibitor. However, it is unknown in aortic vascular response, therefore, we hypothesized that A2AAR-gene deletion in mice (A2AAR−/−) affects adenosine-induced vascular response by increase in sEH and adenosine A1 receptor (A1AR) activities. A2AAR−/− mice showed an increase in sEH, AI 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 A2AAR−/− vs. C57Bl/6 mice. In A2AAR−/−, NECA and CCPA-induced increase in dose-dependent vasoconstriction compared to C57Bl/6 mice. However, NECA and CCPA-induced dose-dependent vascular contraction in A2AAR−/− was reduced by t-AUCB with NECA. Similarly, dose-dependent vascular contraction in A2AAR−/− was reduced by t-AUCB with CCPA. In addition, Ang-II enhanced NECA and CCPA-induced dose-dependent vascular contraction in A2AAR−/− with NECA. Similarly, the dose-dependent vascular contraction in A2AAR−/− was also enhanced by Ang-II with CCPA. Further, t-AUCB reduced Ang-II-enhanced NECA and CCPA-induced dose-dependent vascular contraction in A2AAR−/− mice. Our data suggest that the dose-dependent vascular contraction in A2AAR−/− mice depends on increase in sEH, A1AR and CYP4A protein expression.