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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2010; 56(4): 76-85

The role of mitochondria in NO-dependent regulation of Na+, K+ -ATP activity in the rat aorta

Akopova OV, Kotsiuruba AV, Kharlamova OM, Korkach IuP, Sahach VF

  1. O.O. Bogomoletz Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv, Ukraine
  2. A.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine


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+-AT-Pase 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 decomposi-tion 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-radi-cal. 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.

Keywords: Na+, K+ -ATPase, aorta, Ca2+-uptake, heart mitochondria, ROS, RNS, oxidative damage


  1. Akopova OV, Kotsyuruba AV, Tkachenko YP, Sagach VF Nitric oxide inhibits the opening of the mitochondrial pore and increases the calcium capacity of the mitochondria in vivo . Fiziol zh. 2005. 51, N 3. p. 3-11.
  3. Akopova OV, Kharlamova OM, Kotsyuruba AV, Ko + kach Yu.P., Sagach VF The influence of nitric oxide on Na, K + ATPase in the aortic tissue of rats . Fiziol zh. 2009. 55, N 1. p. 27-35.
  5. Akopova O.V. Rol' mitohondrial'noi pori v transmembrannom obmene kal'tsiya v mitohondriyah . . Ukr.biohim. zhurn. 2008. 80, N 3. S.40-47.
  7. Boldirev A.A. Na+, K+-ATRaza kak oligomernii ansambl' .Biohimiya. 2001. 66. S.1013-1025.
  9. Vanin A.F. Dinitrozil'nie kompleksi zheleza i S-nitrozotioli dve vozmozhnie formi stabi­lizatsii i transporta oksida azota v biologicheskih sistemah . Biohimiya, 1998. 63, N 7. S.924-938.
  11. Korkach Yu.P., Dudchenko N.O., Kotsyuruba A.V., Prisyazhna O.D., Sagach V.F.. Rol' negemovogo zaliza u protektornii dii ekdisteronu na rozvitok streptozototsin-indukovanoi gipoglikemii u shchuriv . Ukr.biohim. zhurn. 2008. 80, N 1. S.46-51.
  13. Kostyuk P.G., Kostyuk O.P.,  Luk'yanets' O.A. Calcium ions in brain function from physiology to pathology.  K.: Nauk. dumka.  2005. 198 p.
  15. Skulachev V.P. Energetika biologicheskih membran. M.: Nauka, 1989. 564 s.
  17. Acuna-Castroviejo D., Martin M., Macias M., Escames G., Leon J., Khaldy H., Reiter R.J. Melatonin, mito­chondria, and cellular bioenergetics .J. Pineal Res. 2001. 30. P.65-74. CrossRef PubMed
  19. Basaga H.S. Biochemcal aspects of free radicals .Cell Biol. 1990. 68,N 5. P.989-998. CrossRef PubMed
  21. Blaustein M.P. Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness . Amer. J. Physiol. 1993. 264. P. C1367-C1387. CrossRef PubMed
  23. Brown G.C. Nitric oxide and mitochondrial respiration .Biochim. Biophys. Acta. 1999. 1411. P.351-369. CrossRef  
  24. Conte D., Narindrasorosa K.S., Sarcar B. In vivo and in vitro iron-replaced zinc finger generated free radicals and caused DNA damage . J. Biol. Chem. 1996. 271,N 9. P.5125-5130. CrossRef PubMed
  26. Daiber A., Wenzel P., Oelze M., Schuhmacher S., Jansen T., Munzel T. Mitochondrial aldehyde dehydrogenase (ALDH-2) maker of and marker for nitrate tolerance in response to nitroglycerine treatment . Chem. Biol. Interact. 2009. 178, N 1-3. P. 40-47. CrossRef PubMed
  28. Frieden M., James D., Castelbou C. Danckaert A.., Martinon J. C, Demareux N. Calcium homeostasis during mitochondrial fragmentation and perinuclear clustering induced by hFis1 . J. Biol. Chem. 2004. 279. P.22704-22714. CrossRef PubMed
  30. Green L.C., David A.W., Glogovski J. Analysis of ni­trate, nitrite and [15N]nitrate in biological fluids . Anal. Biochem. 1982. 126, N 1. P.131-138. CrossRef  
  31. Huwiler M., Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase. HO. iodide system . Eur. J. Biochem., 1984. 141, N 1. P. 69-74. CrossRef PubMed
  33. Ignarro L.J., Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide . Circulat. Res. 2002. 90, N 1. P.21-28. CrossRef PubMed
  35. Lander H.M. An essential role for free radicals and derived species in signal transduction . FASEB J. 1997. 11. P.118-124. CrossRef PubMed
  37. Patchornik G., Goldshleger R., Karlish S.J.D. The complex ATP-Fe2+ serves as a specific affinity cleavage reagent in ATP-Mg+ sites of Na, K-ATPase: altered ligation of Fe2+(Mg2+) ions accompanies the E1P^E P conformational change .Proc. Natl. Acad. Sci. USA. 2000. 97, N 22. P.1 1954-11959. CrossRef PubMed PubMedCentral
  39. Pfeiffer S., Gorren A.C.F., Schmidt K., Wermer E.R., Hansert B., Bohle D.S., Mayer B. Metabolic fate of peroxynitrite in aqueous solution. Reaction with nitric oxide and pH-dependent decomposition to nitrite and oxygen in 2:1 stoichiometry. J. Biol. Chem. 1997. 272, N 6. P.3465-3470. CrossRef PubMed
  41. Rizzuto R., Bernardi P., Pozzan T. Mitochondria as all-round players of the calcium game . J. Physiol., 2000. 529, N 1. P. 37-47. CrossRef PubMed PubMedCentral
  43. Rizzuto R., Pinton P., Carrington W., Fay F.S., Fogarty K.E., Lifshitz L.M., Tuft R.A., Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mi­tochondrial Ca2+ responses . Science. 1998. 280. P.1763-1766. CrossRef PubMed
  45. Rossi C.S., Bielawsky J., Lehninger A.L. Separation of H+ and OH- in the extramitochondrial and mitochon­drial phases during Ca2+-activated electron transport . . J. Biol. Chem. 1966. 241, N 8. P.1919-1921.

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