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 (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.
Krylova
Irina B
IB
Institute of Experimental Medicine, Russian Academy of Medical Sciences, St Petersburg 197376, Russian Federation.
Kachaeva
Evgeniya V
EV
Rodionova
Olga M
OM
Negoda
Alexander E
AE
Evdokimova
Nataliya R
NR
Balina
Maria I
MI
Sapronov
Nikolay S
NS
Mironova
Galina D
GD
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014529:Uridine / Q000494:pharmacology*; D014530:Uridine Diphosphate / Q000494:pharmacology; D014542:Uridine Monophosphate / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D014530:Uridine Diphosphate; D014542:Uridine Monophosphate; D014529:Uridine