Inhibition or deletion of Adenosine A2Areceptor enhances acetylcholine‐induced vascular response: role of angiotensin‐II in A2AAR‐/‐ vs. C57Bl/6 mice

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