Hydrogen Sulfide (H 2 S): A Novel Mediator in Adenosine A 2A Receptor‐induced Vasorelaxation

Previously, we have shown that adenosine-induced aortic relaxation occurs through activation of A2A adenosine receptor (AR) via opening of KATP channels (Ponnoth et al., 2009, 2012). In this study, we investigated whether H2S, an endogenous gaseous mediator of vasorelaxation, contributes to A2A-induced aortic relaxation. Organ bath and western blot experiments were done using isolated aortas from A2AKO and WT mice. H2S donor sodium hydrosulfide (NaHS; 10-3M) produced significantly higher relaxation in WT aorta compared to A2AKO (54.63±2.14% vs.17.16±5.84%). Removal of endothelium had no effect on NaHS responses in WT and A2AKO, neither were responses different in A1KO or A2BKO compared to WT. KATP blocker glibenclamide significantly inhibited NaHS responses in both WT (from relaxation of 54.63±2.14% to contraction of 17.76±6.46%) and A2AKO (from relaxation of 17.16±5.84% to contraction of 52.43±9.23%) and this effect was more pronounced in A2AKO. Non-selective adenosine analog NECA (10-5M) response in WT ...