(944.2) Inhibition or deletion of Adenosine A2A receptor enhances acetylcholine-induced vascular response: role of angiotensin-II in A2AAR-/- vs. C57Bl/6 mice

Poster Board Number: B201

Stephanie Agba (West Virginia University), Ahmad Hanif (West Virginia University), Catherine Ledent (IRIBHN Universite Libre de Bruxelles, Belgium), Tilley Stephen (University of North Carolina at Chapel Hill), Mohammed Nayeem (West Virginia University)

In previous studies, we showed that adenosine-induced vascular relaxation was reduced in adenosine A2A receptor (A2AAR)-null (A2AAR-/-) or A2AAR-inhibited C57Bl/6 mice. However, it is unknown the acetylcholine-induced vascular response in A2AAR-/- or A2AAR-inhibited C57Bl/6 mice; therefore, we hypothesized that the acetylcholine enhances endothelial-dependent vascular relaxation in A2AAR-gene deleted (A2AAR-/-) or inhibited C57Bl/6 mice compared to their respective controls. Acetylcholine-induced dose dependent vascular response was tested with SCH58261 (A2AAR-antagonist) in C57Bl/6 vs. non-treated C57Bl/6 mice and angiotensin-II (Ang-II) in C57Bl/6 vs. non-treated C57Bl/6 mice, Ang-II treated A2AAR-/- vs. non-treated A2AAR-/- mice and Ang-II treated A2AAR-/- vs. Ang-II treated C57Bl/6 mice. In C57Bl/6 mice, SCH58261 (1µM) increased in acetylcholine-induced dose-dependent vascular relaxation compared to non-treated C57Bl/6 mice. Similarly, in A2AAR-/- mice, acetylcholine enhanced dose-dependent vascular relaxation compared to C57Bl/6 mice. However, acetylcholine-induced dose-dependent vascular relaxation was reduced with angiotensin-II (Ang-II,1µM) in C57Bl/6 compared to non-treated C57Bl/6 mice and acetylcholine-induced dose-dependent vascular relaxation was reduced with Ang-II (1µM) in C57Bl/6 compared to A2AAR-/- treated mice. Our data suggest that the acetylcholine dose-dependent vascular relaxation is endothelial dependent and is enhanced in the absence or inhibition of A2AAR unlike adenosine dose-dependent vascular relaxation in mice.

The authors report that there are no conflicts of interest.
National Institutes of Health (HL-114559) to M. A. Nayeem supported this work.