Effects of A3 adenosine receptor activation and gene knock-out in ischemic-reperfused mouse heart

摘要: Objectives : To characterize effects of A3 adenosine receptor (A3AR) activation and gene knock-out on responses to ischemia-reperfusion in mouse heart. Methods Perfused hearts from wild-type A3AR (A3AR KO) mice were subjected 20 min ischemia 30 reperfusion. Functional assessed changes energy metabolism cytosolic pH monitored via 31P-NMR spectroscopy. Results Selective agonism with 100 nM 2-chloro- N 6-(3-iodobenzyl)-adenosine-5′- -methyluronamide (chloro-IB-MECA) enhanced post-ischemic contractile recovery without altering contracture development hearts, an effect unrelated non-selective A1 or A2 receptors. Chloro-IB-MECA also improved overexpressing A1ARs. Paradoxically, was by KO. Developed pressure, +d P /d t , −d all recovered higher levels KO (70–80% pre-ischemia) vs. (45–50% ( <0.05). Enhanced recoveries ATP, phosphocreatine (PCr), inorganic phosphate (Pi), state ([ATP]/[ADP]. [Pi], Δ G ATP) pH. Conclusions is cardioprotective A1ARs, yet deletion generates ischemia-tolerant phenotype This may be due compensatory undefined genotypic differences hearts.