1. Academic Validation
  2. The cardioprotective effect of uridine and uridine-5'-monophosphate: the role of the mitochondrial ATP-dependent potassium channel

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

  • Exp Gerontol. 2006 Jul;41(7):697-703. doi: 10.1016/j.exger.2006.03.005.
Irina B Krylova 1 Evgeniya V Kachaeva Olga M Rodionova Alexander E Negoda Nataliya R Evdokimova Maria I Balina Nikolay S Sapronov Galina D Mironova
Affiliations

Affiliation

  • 1 Institute of Experimental Medicine, Russian Academy of Medical Sciences, St Petersburg 197376, Russian Federation.
Abstract

The activity of mitochondrial ATP-dependent Potassium Channel (mitoKATP) 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 mitoKATP activation provides cardioprotection. We demonstrated that uridine-5'-diphosphate (UDP) possesses the property to activate mitoKATP. At a concentration of 30 microM, 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. MitoKATP prevents mainly ischemic injuries and partially rhythm disorders.

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