Publicou 4 edições por ano
ISSN Imprimir: 2155-014X
ISSN On-line: 2155-0158
The Role of Mitochondria in the NO-Dependent Regulation of Na+/K+-ATPase Activity in Rat Aorta
RESUMO
The interaction is studied in vivo between two ion-transporting machineries of cardiovascular system - Na+/K++-ATPase of rat aorta and Ca2+-uptake system of mitochondria in short-term response to different doses of NO donor, nitroglycerine (NG). Activity of Na+/K+-ATPase was determined in rat aorta, and mitochondrial uptake of Ca2+ was studied in rat heart mitochondria assuming that metabolism induced by NO in cardiac mitochondria is similar to that of mitochondria from rat aorta. The data show coordinated dose-dependent action of NG on Na+/K+-ATPase activity as well as Ca2+-uptake in mitochondria. An activation of Na+/K+-ATPase by low dose of NG (0,25 mg/kg body weight) is accompanied by the activation of Ca2+-uptake in mitochondria as a result of inhibition of permeability transition pore. But further increase of the dose of the drug leads to reciprocal changes of studied parameters: the decrease in Na+-pump activity below control level and the increase of Ca2+-uptake in mitochondria with a peak at 1,0 mg/kg NG, which takes place in parallel with dramatic rise in the level of ROS and RNS together with their toxic products, nitrosothiols (NT) and free iron (Fe2+) content in mitochondria. Strong correlation between Ca2+-uptake and Fe2+-release, Fe2+-release and OH-radical formation, the rise in OH-radical level and the decrease of that of H2O2 and mitochondrial NT together with the inhibition of Na+/K+-ATPase favor a hypothesis that oxidative stress in rat aorta is of mitochondrial origin due to enhanced uptake of Ca2+ into mitochondrial matrix, Fe2+ deliverance and manifold increase in ˙OH-radical formation from decomposition of hydroperoxide in Haber-Weiss reaction and the decomposition of mitochondrial NT via formation of peroxynitrite, both catalyzed by Fe2+, with subsequent release of OH-radical. Effective abolition of Na+/K+-ATPase inhibition by potent antioxidant melatonin gives the evidence of the oxidative nature of Na+/K+-ATPase inhibition by nitric oxide in rat aorta.