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

Abstract

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 μM, it reactivated mitoK ATP 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.