The cardioprotective effect of uridine and uridine-5′-monophosphate:: The role of the mitochondrial ATP-dependent potassium channel

The activity of mitochondrial ATP-dependent potassium channel (mitoK(ATP)) of rat heart and liver mitochondria was shown to decrease during aging. This partially explains the increase of risk of ischemia at a mature age since mitoK(ATP) activation provides cardioprotection. We demonstrated that uridine-5'-diphosphate (UDP) possesses the property to activate mitoK(ATP). At a concentration of 30 mu M, it reactivated mitoKATP in mitochondria, and 5-hydroxydecanoate (5-HD) eliminated this effect. In experimental animals. UDP precursors Uridine and uridine-5'-monophosphate (UMP) (both 30 mg/kg, administered intravenously 5 min before coronary Occlusion) decreased the myocardium ischemic alteration index (1.9 and 3.5 times, respectively) and the T-wave amplitude within 60 min after occlusion. Both effects were inhibited by Glibenclamide (Glib) and 5-HD. UMP and uridine decreased the number of premature ventricular beats 5.6 and 1.9 times and the duration of ventricular tachycardia 9.4 and 4.1 times, respectively. Glib and 5-HD inhibited the anti-arrhythmic parameters. 5-HD being less effective. Uridine and UMP decreased the duration of fibrillation 10.8 and 3.6 times, respectively, and this effect was not abolished by Glib and 5-HD. Thus, uridine and UMP, which are the precursors of UDP in the cell, possess cardioprotective properties. MitoK(ATP) prevents mainly ischemic injuries and partially rhythm disorders. (c) 2006 Elsevier Inc. All rights reserved.