Effect of KATP channels opener pinacidil on functioning of liver mitochondria of rats with different resistance to hypoxia under stress conditions
We have examined the influence of ATP-sensitive potassium (КATP) channel opener pinacidil (0.06 mg/kg) and inhibitor glibenclamide (1 mg/kg) on the changes of energy metabolism in the liver of rats under the stress conditions. The rats were divided in two groups with high and low resistance to hypoxia. The stress was modeled by placing the rats in a cage filled with water and closed with a net. The distance from water to the net was only 5 cm. The effects of КATP opener pinacidil (0.06 mg/kg) and inhibitor glibenclamide (1 mg/kg) on ADP-stimulating mitochondrial respiration by Chance, calcium capacity of organellas and processes of lipid peroxidation in the liver of rats with different resistance to hypoxia under the stress condition have been investigated. We have used the next substrates of oxidation: 0.35 mM succinate and 1 mМ apha-ketoglutarate. The additional analyses were conducted with the use of inhibitors: mitochondrial enzyme complex I 10 mМ rotenone and succinate dehydrohenase 2 mМ malonic acid. It was shown that the stress condition evoked the succinate oxidation and the decrease of ?-ketoglutarate efficacy, the increase of calcium mitochondrial capacity and the intensification of lipid peroxidation processes. Under the presence of succinate, the increase of O2 uptake with simultaneous decrease of ADP/O ratio in rats with high resistance under stress was observed. Simultaneously, oxidation of ?-ketoglutarate, a NAD-dependent substrate, was inhibited. Pinacidil caused the reorganization of mitochondrial energy metabolism in favour of NAD-dependent oxidation and the improvment of the protection against stress. The decrease of the efficacy of mitochondrial energy processes functioning was shown in animals with low resistance to hypoxia. КATP channel opener pinacidil has a protective effect on the processes of mitochondrial liver energy support under stress. These changes deal with the increase of ?-ketoglutarate oxidation (respiratory rate and ADP/O) and the decrease of lipid peroxidation processes. We concluded about protective effect of pinacidil on mitochondrial functioning under stress.
Published at the site: 2004-02-02
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