[The role of mitochondria in NO-dependent regulation of Na+, K+ -ATP activity in the rat aorta].
In experiments in vivo we studied the interaction between two ion-transporting mechanisms 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). The activity of the 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 in rat aortic mitochondria. The data show a 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. However, further increase of the dose of the drug leads to reciprocal changes of studied parameters: the decrease in Na+ -pump activity below the 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 the 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 an 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 catalysed by Fe2+, with subsequent release of *OH-radical. Effective abolition of Na+, K+ -ATPase inhibition by potent antioxidant melatonine gives the evidence of the oxidative nature of Na+, K+ -ATPase inhibition by nitric oxide in rat aorta.
O V
OV
Akopova
A V
AV
Kotsiuruba
O M
OM
Kharlamova
Iu P
IuP
Korkach
V F
VF
Sahach
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors; D000083162:Mitochondrial Permeability Transition Pore; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000975:Antioxidants; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007501:Iron; D000254:Sodium-Potassium-Exchanging ATPase; D005996:Nitroglycerin; D008550:Melatonin; D002118:Calcium