Tkachenko H M, Kurhaliuk N M, Vovkanych L S
Ukr Biokhim Zh (1999). 2004 Jan-Feb;76(1):56-64.
We have examined the influence of ATP-sensitive potassium (KATP) 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 KATP 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 mM alpha-ketoglutarate. The additional analyses were conducted with the use of inhibitors: mitochondrial enzyme complex I 10 mM rotenone and succinate dehydrohenase 2 mM malonic acid. It was shown that the stress condition evoked the succinate oxidation and the decrease of alpha-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 alpha-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. KATP channel opener pinacidil has a protective effect on the processes of mitochondrial liver energy support under stress. These changes deal with the increase of alpha-ketoglutarate oxidation (respiratory rate and ADP/O) and the decrease of lipid peroxidation processes. We concluded about protective effect ofpinacidil on mitochondrial functioning under stress.
我们研究了ATP敏感性钾（KATP）通道开放剂吡那地尔（0.06 mg/kg）和抑制剂格列本脲（1 mg/kg）对处于应激状态下大鼠肝脏能量代谢变化的影响。将大鼠分为对缺氧具有高抗性和低抗性的两组。通过将大鼠置于装满水并用网封闭的笼子中来模拟应激。水到网的距离仅为5厘米。研究了KATP开放剂吡那地尔（0.06 mg/kg）和抑制剂格列本脲（1 mg/kg）对应激状态下对缺氧具有不同抗性的大鼠肝脏中由Chance法测定的ADP刺激的线粒体呼吸、细胞器的钙容量以及脂质过氧化过程的影响。我们使用了以下氧化底物：0.35 mM琥珀酸和1 mMα-酮戊二酸。使用抑制剂进行了额外的分析：线粒体酶复合物I的10 mM鱼藤酮和琥珀酸脱氢酶的2 mM丙二酸。结果表明，应激状态引起了琥珀酸氧化以及α-酮戊二酸功效的降低、线粒体钙容量的增加和脂质过氧化过程的加剧。在存在琥珀酸的情况下，观察到应激状态下高抗性大鼠的氧气摄取增加，同时ADP/O比值降低。同时，NAD依赖性底物α-酮戊二酸的氧化受到抑制。吡那地尔导致线粒体能量代谢重组，有利于NAD依赖性氧化，并改善了对应激的保护作用。低抗缺氧性动物显示出线粒体能量过程功能效率的降低。KATP通道开放剂吡那地尔对应激状态下肝脏线粒体能量支持过程具有保护作用。这些变化涉及α-酮戊二酸氧化的增加（呼吸速率和ADP/O）以及脂质过氧化过程的减少。我们得出结论，吡那地尔对应激状态下的线粒体功能具有保护作用。
