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

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Abstract

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.

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Acknowledgements

This work supported by National Institutes of Health Grant HL-114559 to M. A. Nayeem, we are very much thankful to Ms. Brandy J. Wilmoth, B.S., RVT (Biology Technician) for performing tissue bath experiments.

Funding

National Institutes of Health (HL-114559) to M. A. Nayeem supported this work.

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Authors and Affiliations

  1. Pharmaceutical Sciences, School of Pharmacy, Center for Basic and Translational Stroke Research, West Virginia University Morgantown, Morgantown, WV, USA

    Ahmad Hanif, Stephanie O. Agba & Mohammed A. Nayeem

  2. IRIBHN, Universite Libre de Bruxelles, Bruxelles, Belgium

    Catherine Ledent

  3. Division of Pulmonary and Critical Care Medicine, UNC at Chapel Hill, Chapel Hill, NC, USA

    Stephen L. Tilley

  4. University of California at Davis, One Shields Avenue, Davis, CA, USA

    Christophe Morisseau

  5. Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd floor, Room # 220, Health Science Center – North, 1 Medical Center Drive, PO Box 9530, Morgantown, WV, 26506-9530, USA

    Mohammed A. Nayeem

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  1. Ahmad Hanif
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  2. Stephanie O. Agba
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MAN conception, design of research, performing experiments, analysis drafting and editing; AH and SA were cooperating in the experimentations, reading, correction, editing and input; CL and SLT provided transgenic mice; CM provided the t-AUCB.

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Correspondence to Mohammed A. Nayeem.

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Hanif, A., Agba, S.O., Ledent, C. et al. Adenosine A2A receptor and vascular response: role of soluble epoxide hydrolase, adenosine A1 receptor and angiotensin-II. Mol Cell Biochem 476, 1965–1978 (2021). https://doi.org/10.1007/s11010-021-04049-w

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