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Adenosine A 2A Receptor and Vascular Response: Role of Soluble Epoxide Hydrolase, Adenosine A 1 Receptor and Angiotensin‐II
Author(s) -
Agba Stephanie,
Hanif Ahmed,
Ledent Catherine,
Tilley Stephen,
Morisseau Christophe,
Itani Hana
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02369
Subject(s) - ccpa , epoxide hydrolase 2 , medicine , adenosine , endocrinology , adenosine receptor , angiotensin ii , agonist , receptor , chemistry , biochemistry , enzyme
Previously, we reported that the coronary reactive hyperemic response (CRH) was reduced in adenosine A 2A receptor‐null (A 2A AR ‐/‐ ) mice, and reversed by soluble epoxide hydrolase (sEH) inhibitor. However, this 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 increasing 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. Furthermore, 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.