, Volume 39, Issue 4–5, pp 343–346 | Cite as

Changes in the mitochondrial permeability in medullary cardiovascular neurons influence the hemodynamics in rats

  • L. N. Shapoval
  • O. V. Dmytrenko
  • L. S. Pobegailo
  • L. G. Stepanenko
  • V. F. Sagach


In acute experiments on anesthetized rats, we studied the effects of modulation of the mitochondrial permeability in medullary cardiovascular neurons (nucl. tractus solitarii, NTS, nucl. ambiguus, AMB, paramedian reticular nucleus, PMn, and lateral reticular nucleus, LRN) on the systemic arterial pressure (SAP). We were the first to show that the mitochondrial permeability is essential for medullary cardiovascular control. An increase in the mitochondrial permeability with injections of an inductor of mitochondrial transition pore opening, phenylarsine oxide (PAO, 0.5 to 504 nmol), into the medullary nuclei resulted in long-lasting decreases in the SAP; at high doses of PAO, these drops could be irreversible and led to the animal’s death. Injections of an inhibitor of mitochondrial transition pore opening, melatonin (0.7 to 70.0 nmol), into the medullary nuclei induced dose-dependent increases in the SAP. Melatonin and L-arginine were shown to demonstrate neuroprotective effects due to their ability to attenuate the consequences of increased mitochondrial permeability in medullary cardiovascular neurons.


mitochondrial permeability transition pore medullary neurons cardiovascular control 


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  1. 1.
    G. Kroemer, B. Dallsports, and M. Resce-Rigon, “The mitochondrial death/life regulator in apoptosis and necrosis,” Annu. Rev. Physiol., 60, 619–642 (1998).PubMedCrossRefGoogle Scholar
  2. 2.
    M. Zoratti, I. Szabo, and U. De Marchi, “Mitochondrial permeability transitions: how many doors to the house?” Biochim. Biophys. Acta, 1706, 40–52 (2005).PubMedCrossRefGoogle Scholar
  3. 3.
    M. Crompton, “The mitochondrial permeability transition pore and its role in cell death,” Biochem. J., 34, 233–249 (1999).CrossRefGoogle Scholar
  4. 4.
    G. Kroemer and J.C. Reed, “Mitochondrial control of cell death,” Nat. Med., 6, 513–519 (2000).PubMedCrossRefGoogle Scholar
  5. 5.
    I. Hillered, B. K. Siesjo, and K. Arfors, “Mitochondrial response to transient forebrain ischemia and recirculation in rat,” J. Cerebr. Blood Flow Metab., 4, 438–446 (1984).Google Scholar
  6. 6.
    K. Allen, A. Almeida, T. Bates, and J. Clark, “Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia,” J. Neurochem., 64, 2222–2229 (1995).PubMedCrossRefGoogle Scholar
  7. 7.
    A. Almeida, K. I. Allen, T. E. Bates, and J. B. Clark, “Effect of reperfusion following cerebral ischaemia on the activity of the mitochondrial respiratory chain in the gerbil brain,” J. Neurochem., 65, 1698–1703 (1995)PubMedCrossRefGoogle Scholar
  8. 8.
    S. Javadov and M. Karmazyn, “Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as putative target for cardioprotection,” Cell. Physiol. Biochem., 20, Nos. 1/4, 1–22 (2007).PubMedCrossRefGoogle Scholar
  9. 9.
    L. N. Shapoval, V. F. Sagach, and L. S. Pobegailo, “Nitric oxide influences ventrolateral medullary mechanisms of vasomotor control in the cat,” Neurosci. Lett., 132, 47–50 (1991).PubMedCrossRefGoogle Scholar
  10. 10.
    J. Zanzinger, “Role of nitric oxide in neural control of cardiovascular functions,” Cardiovascul. Res., 43, 639–649 (1999)CrossRefGoogle Scholar
  11. 11.
    S. Chowdhary and N. Townend, “Role of nitric oxide in the regulation of cardiovascular autonomic control,” Clin. Sci., 97, 5–17 (1999).PubMedCrossRefGoogle Scholar
  12. 12.
    T. I. Krukoff, “Central actions of nitric oxide in regulations of autonomic functions,” Brain. Res., 30, 52–65 (1999).CrossRefGoogle Scholar
  13. 13.
    I. N. Mungrue, D. S. Bredt, D. J. Stewart, and M. Hasain, “From molecules to mammals: what’s NOS got to do with it?” Acta Physiol. Scand., 179, 123–135 (2003).PubMedCrossRefGoogle Scholar
  14. 14.
    I. J. Ignarro, Nitric Oxide: Biology and Pathology, Academic Press, San Diego (2000).Google Scholar
  15. 15.
    P. S. Brookes, E. P. Salimas, K. Darley-Usmar, et al., “Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release,” J. Biol. Chem., 275, 20474–20479 (2000).PubMedCrossRefGoogle Scholar
  16. 16.
    J. J. Poderoso, M. C. Carreas, C. Lisdero, et al., “NO inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles,” Arch. Biochem. Biophys., 328, 83–92 (1996).CrossRefGoogle Scholar
  17. 17.
    M. A. Packer and M. P. Murphy, “Peroxynitrite causes calcium efflux from mitochondria which is prevented by cyclosporin A,” FEBS Lett., 345, 237–240 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    V. Borutaite, R. Morkuniene, and G. C. Brown, “Release of cytochrome c from heart mitochondria is induced by high calcium and peroxynitrite and is responsible for calcium-induced inhibition of substrate oxidation,” Biochem. Biophys. Acta, 1453, 41–48 (1999).PubMedGoogle Scholar
  19. 19.
    G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, New York (1982).Google Scholar
  20. 20.
    D. R. Green, “Apoptotic pathways: ten minutes to death,” Cell, 121, 671–674 (2005)PubMedCrossRefGoogle Scholar
  21. 21.
    A. P. Halestrap, S. J. Clarke, and S. A. Javadov, “Mitochondrial permeability transition pore opening during myocardial reperfusion — a target for cardioprotection,” Cardiovasc. Res., 61, 372–385 (2004).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • L. N. Shapoval
    • 1
  • O. V. Dmytrenko
    • 1
  • L. S. Pobegailo
    • 1
  • L. G. Stepanenko
    • 1
  • V. F. Sagach
    • 1
  1. 1.Bogomolets Institute of PhysiologyNational Academy of Sciences of UkraineKyivUkraine

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