Clinical & Experimental Cardiology

Biography

Biography: S Jamal Mustafa

Abstract

Adenosine increases coronary flow (CF) through the activation of A_2A and A_2B adenosine receptors (ARs). However, these mechanisms are not fully understood. We previously showed that adenosine-induced increase in CF is in part through NADPH oxidase (Nox), which is independent of A₁ or A₃ ARs. In this study, we hypothesize that adenosine-mediated increase in CF is through Nox activation and depends on A_2A but not on A_2B ARs. Functional studies were conducted using Langendorff mouse hearts. Hydrogen peroxide (H₂O₂) production was measured in isolated coronary arteries from WT, A_2A and A_2B AR KO mice using immunofluorescence. Adenosine-induced concentration-dependent increase in CF was attenuated by the specific Nox2 inhibitor gp91 ds-tat or reactive oxygen species (ROS) scavenger EUK134 in both WT and A_2B but not A_2A AR KO hearts. Similarly, the A_2A AR selective agonist CGS-21680-induced increase in CF was significantly blunted by Nox2 inhibition in both WT and A_2B AR KO, while the A_2B AR selective agonist BAY 60-6583-induced increase in CF was not affected by Nox2 inhibition in WT. In intact isolated coronary arteries, adenosine-induced (10 μM) increase in H₂O₂ formation in both WT and A_2B AR KO mice was attenuated by Nox2 inhibition, whereas adenosine failed to increase H₂O₂ production in A_2A AR KO mice. In conclusion, adenosine-induced increase in CF is partially mediated by Nox2-derived H₂O₂, which critically depends upon the presence of A_2A AR. These studies may lead to better understanding of the role of ARs in coronary disease and may lead to better therapeutic approaches.