Acetylcholine Exerts Cardioprotection by Reducing Reactive Oxygen Species

To determine whether modulating reactive oxygen species (ROS) release by mitochondrial is involved in the cardioprotection exerted by acetylcholine (ACh). In isolated ventricular myocytes from male Sprague-Dawley rats, 0.1 μM ACh was administered for 6 min before 60 min of simulated ischemia and 30 min of reoxygenation or reperfusion (I/R). A mitochondrial ATP-sensitive potassium channel (mitoKATP channel) inhibitor (5-hydroxydecanoate, 5-HD) and a mitochondrial permeability transition pore MPTP opener (atractyloside, Atr) were used to analyze the pathways underlying the effect of ACh. At the end of reperfusion, we found that pretreatment with ACh markedly reduced I/R induced cell death, lactate dehydrogenase (LDH) release and ROS signals. However, 100 μM 5-HD for 20 min before ischemia or 20 μM Atr for 20 min at the beginning of reperfusion attenuated this effect of ACh. The results indicate that ACh may protect the isolated ventricular myocyte against ischemia and reperfusion injury by inhibiting ROS signals through mitoKATP-MPTP pathway.