Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

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. 2012; 58(6): 3-8


Increase in the sensitivity of the mitochondrial permeability transition pore opening to Ca2+ in heart of spontaneous hypertensive rat

Strutyns'ka NA, Dorofeieva NO, Vavilova HL, Sahach VF.

    O.O. Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz58.06.003

Abstract

In experiments vitro on the mitochondria isolated from adult and spontaneous hypertensive rat hearts, we studied the sensitivity of the mitochondrial permeability transition pore (mPTP) opening to its natural inductor, Ca2+. We observed an increase in the sensitivity of mPTP opening to Ca2+ in the heart of spontaneous hypertensive rats because of a decrease in the threshold concentration of this ion required for organ-elles swelling by two orders of magnitude. It was shown that the classical inhibitor mPTP cyclosporin A (10-5 mol / L) partially (54%) inhibited of mPTP opening in the heart of these animals, indicating that the presence in the heart of these animals of cyclosporin A-insensitive component of the mPTP. The results of our observations give reason to conclude that the hypertensive state of the organism is associated with mitochondrial dysfunction, which is characterized, in par­ticular, by an increased sensitivity mPTP to Ca2+, eliciting a widespread tissue damage and diseases of the cardiovascular system, especially hypertension.

Keywords: mitochondrial permeability transition pore, heart,hypertension, rat.

References

  1. Gorbass IM Epidemiology of the main risk factors for cardiovascular disease . Arterial hypertension. 2008. N 2. P. 13-18. CrossRef PubMed
  2.  
  3. Postnov Yu.V. Insufficiency of ATP formation in connection with calcium overload of mitochondria as a source of increase in blood pressure in primary hypertension . Cardiology. 2005. N 10. pp. 4-11.
  4.  
  5. Postnov YV, Orlov SN Primary hypertension as a pathology of cell membranes. M: Medicine. 1987. 192 p.
  6.  
  7. Sagach VF, Vavilova GL, Strutinskaya NA, Rudik OV Aging Increases Sensitivity to Mitochondrial Pore Inductors in the Heart of Rats . Physiol. . 2004. 50, N 2. P.49-63.
  8.  
  9. Sirenko Yu.M. Hypertension and arterial hypertension. Donetsk: Publisher Zaslavsky O.Yu., 2011. 304 p.
  10.  
  11. Caldern-Cortsa E., Cort?s-Rojoa C., Clemente-Guerreroa M., Manzo-?valosa S., Villalobos-Molinab R., Boldoghc I., Saavedra-Molinaa A. Changes in mitochondrial functio­nality and calcium uptake in hypertensive rats as a function of age . Mitochondrion. 2008. 8, N 3. P. 262-272. CrossRef PubMed PubMedCentral
  12.  
  13. Di Lisa F., Carpi A., Giorgio V., Bernardi P. The mitochondrial permeability transition pore and cyclophilin D in cardioprotection . Biochimet Biophys Acta. 2011. 1813, N 7. R. 1316-1322. CrossRef PubMed
  14.  
  15. Halestrap A.P., Mc Stray G.P., Clarke S.J. The permeability transition pore complex: another view . Biochemie. 2002. 84. P.153-166. CrossRef  
  16. Hamet P., Richard L.T., Dam T.V. Apoptosis in target organs of hypertension. Hypertension. 1995. 26. R. 642-648. CrossRef PubMed
  17.  
  18. He L., Lemasters J.J. Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function? . FEBS Let. 2002 512. P.1-7. CrossRef  
  19. Javadov S., Karmazyn M., Escobales N. Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases . Pharmacol. Exp. Ther. 2009. 330, N 3 P. 670-678. CrossRef PubMed
  20.  
  21. Lesnefsky E.J., Moghaddas S., Tandler J. Mitochondrial dys­function in cardiac disease: ischemia-reperfusion, aging, and failure . J. Mol. Cardiol. 2001. 33, N 6. P.1065-1089. CrossRef PubMed
  22.  
  23. Lopez-Campistrous A., Hao L., Xiang W., Ton D., Semchuk K., Sander J., Ellison M.J., Fernandez-Patron C. Mitochondrial dysfunction in the hypertension rat brain. Respiratory complexes exhibit assembly defects in hypertension . Hypertension. 2008. 51. R. 412-419. CrossRef PubMed
  24.  
  25. Lucas D.T., Szweda L.I. Cardiac reperfusion injury: aging, lipid peroxidation, and mitochondrial dysfunction . Proc. Natl. Acad. Sci. 1998. 95. P.510-514. CrossRef PubMed PubMedCentral
  26.  
  27. Martel C., Huynh L. H., Garnier A., Ventura-Clapier R., Brenner C. Inhibition of the mitochondrial permeability transition for cytoprotection: direct versus indirect mecha­nisms . Biochem. Res. Inter. 2012. P.1-13. CrossRef PubMed PubMedCentral
  28.  
  29. Ohtsuki T., Matsumoto M., Suzuki K., Taniguchi N., Kamada T. Mitocondrial lipid peroxidation and superoxide dismutase in rat hypertensive target organs . Heart Circulat. Physiol. 1995. 37. R. H1418-H1421. CrossRef PubMed
  30.  
  31. Rasola A., Bernardi P. Mitochondrial permeability tran­sition in Ca2+-dependent apoptosis and necrosis . Cell Calcium. 2011. 50, N 3. R. 222-233. CrossRef PubMed
  32.  
  33. Walther T., Tschope C., Sterner-Kock A., Westermann D., Heringer-Walther S., Riad A., Nikolic A., Wang Y., Ebermann L., Siems W.E., Bader M., Shakibaei M., Schultheiss H.P., Dorner A. Accelerated mitochondrial adenosine di-phosphate. adenosine triphosphate trans­port improves hypertension-induced heart disease . Circulation. 2007. 23. P. 333-344. CrossRef PubMed
  34.  
  35. Wei A. C., Liu T., Winslow R.L., O'Rourke B. Dynamics of matrix-free Ca2+ in cardiac mitochondria: two components of Ca2+ uptake and role of phosphate buffering . J. Gen. Physiol. 2012. 139, N 6. R. 465-478. CrossRef PubMed PubMedCentral
  36.  
  37. Yano T., Miki T., Tanno M., Kuno A., Itoh T., Takada A., Sato T., Kouzu H., Shimamoto K., Miura T. Hypertensive hypertrophied myocardium is vulnerable to infarction and refractory to erythropoietin-induced protection . Hypertension. 2011. 57, N 1. R. 110-115. CrossRef PubMed
  38.  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.