Adenosine A1Receptor Activation Reduces Reactive Oxygen Species and Attenuates Stunning in Ventricular Myocytes

Reactive oxygen species (ROS) formation following brief periods of ischemia or hypoxia is thought to be the underlying cause of myocardial stunning. Adenosine A1receptor activation prior to ischemia/hypoxia attenuates stunning, although the mechanism for this effect remains unknown. Isolated rat ventricular myocytes loaded with the ROS-sensitive indicator dichlorofluorescin were subjected to 30 min glucose-free hypoxia followed by reoxygenation. Intracellular ROS increased 175% (from pre-hypoxic levels) during reoxygenation while cell shortening decreased 50%. In myocytes pretreated with the adenosine A1agonist 2-chloro- N6-cyclopentlyadenosine (CCPA), reoxygenation-induced ROS formation was attenuated by 40% and stunning was attenuated by 50% (compared to untreated myocytes). The mitochondrial KATPchannel opener diazoxide mimicked the effects of CCPA. Pretreatment with the mitochondrial KATPchannel blocker 5-hydroxydecanoate, or the non-selective KATPchannel blocker glibenclamide, blocked the effects of CCPA. These results suggest that adenosine A1receptor activation attenuates stunning by reducing ROS formation. These effects of A1receptor activation appear to be dependent on the opening of KATPchannels.