Українська 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. 2010; 56(1): 62-71


INFLUENCE OF INTRRMITTENT HYPOXIC TRAINING ON HAEMODYNAMIC EFFECTS OF NNOS ACTIVATION IN MEDULLARY CARDIOVASCULAR NEURONS OF RATS

L.M. Shapoval, LS. Pobigailo, LG. Stepanenko, OV. Dmytrenko, VO. Bury, VF. Sagach.

    О.О. Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz56.01.062


Abstract

In our experiments, male Wistar rats, body weight 300 g ± 40 g, were exposed to intermittent hypoxia in a special chamber by its ventilation with hypoxic mixture containing 12% O2 in N2 5 times a day for 15 minutes with 15 min break for 10 days. After completing intermittent hypoxic training, in acute ex­periments on anesthetized with urethane (1.7 g/kg) rats, we studied changes in the systemic arterial pressure (SAP) in­duced by a modulation of neuronal NO-synthase (nNOS) ac-tivity in the neurons of the medullary cardiovascular nuclei (nucleus of tractus solitarius, NTS; nucleus ambiguous, AMB, lateral reticular nucleus, LRN). In control rats housed in normoxic conditions, nNOS activation with injections of L-arginine (5.8 - 58.0 nmol) into the medullary nuclei involved in the cardiovascular control induced the SAP lowering in most experiments in a dose-dependent manner. In rats submitted to intermittent hypoxic training, nNOS activation with injections of L-arginine (5.8 - 58.0 nmol) into the medullary nuclei under study resulted in hypotensive responses which were more expressed as compared with those responses induced by its injections into the medullary nuclei in rats under normoxia. The data obtained give evidence for some additional activation of neuronal NO-synthase in the neurons of the medullary nuclei following intermittent hypoxic training. Effects of nNOS activation were comparable in all the tested nuclei. The effect of nNOS activation was quite short- lasting, it was the most pronounced on the first day after completing hypoxic training. In three days after hypoxic training, injections of L-arginine into tested medullary nuclei resulted in the SAP drop that was similar to that in control animals housed in normoxic conditions. On the contrary, inhibition of nNOS in the neurons induced by injections of NOS-1-antagonist L-NNA (23.0 nmol) into the medullary cardiovascular nuclei resulted in a comparable in­crease in the SAP in both control and hypoxically trained rats. Effects of L-arginine injections into the medullary nuclei were blocked by preliminary administration of a specific nNOS inhibitor 7-nitroindazol. We noticed that intermittent hypoxic training was followed with the SAP elevation observed on the first day after training. Although it was statistically insignificant, and we observed the elevated SAP just after completing hypoxic training, these data provide evidence to support the concept that rats submitted to intermittent hypoxia exhibit an increase in sympathetic activity. The SAP elevation might be also induced by the stressor effect of keeping rats in a chamber to provide hypoxic training. There is an impression that inter­mittent hypoxic training might lead to two simultaneous but opposite directed results: an activation of sympathetic nervous system and an activation of nNOS in the medullary neurons.

Keywords: Intermittent hypoxic training, neuronal NO-syn-thase, medullary cardiovascular neurons.

References

  1. Arkhipenko YV, Sazontova TG, Rozhitskaya II, Meerson FZ The effect of adaptation to periodic hypoxia on the Ca2 + pump of the sarcoplasmic reticulum of the heart and its resistance to endogenous damaging factors . Cardiology. 1992. 32, N 6. P. 57-61.
  2.  
  3. Koshelev VB, Pinelis VG, Vakulin TP Influence of adaptation to high altitude hypoxia on the development of structural changes in resistive vessels of spontaneously hypertensive rats . Cardiology. 1985. 25. p. 80-84.
  4.  
  5. Pshennikova MG, Kuznetsova VA, Kopylov Yu.N. The role of the prostaglandin system in the cardioprotector effect of adaptation to hypoxia in stress . Cardiology. 1992. 32, N 3. p. 61-64.
  6.  
  7. Serebrovskaya TV, Kurgalyuk NM, Nosar B.I., Kolesnikova E.E. Influence of interval hypoxic training and exogenous nitric oxide on energy supply and lipoperoxidation processes in rat liver under acute hypoxia . Fiziol zh. . 2001. 47, N 1. P. 85-92.
  8.  
  9. Shapoval LN, Sagach VF, Pobegailo LS. et al. Participation of nitric oxide in the medullary control of circulatory function in normotensive rats . Neurophysiology. 2002. 34, N 4. P. 294-302.
  10.  
  11. Shapoval LN, Dmitrenko OV, Pobegailo LS Hemodynamic reactions induced by modulation of nitric oxide system activity and permeability of mitochondrial membranes in medullary cardiovascular neurons . Neurophysiology. 2007. 39, N 3. P. 232-244. CrossRef  
  12. Braga V.A., Soriano R.N., Machado B.H. Sympathoexcitatory response to peripheral chemoreflex activa­tion is enhanced in juvenile rats exposed to chronic intermittent hypoxia. Exp. Physiol. 2006. 91. P. 1025-1031. CrossRef PubMed
  13.  
  14. Cai Z., Manalo D.J., Wei G. et al. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circu­lation. 2003. 108. P. 79-85. CrossRef PubMed
  15.  
  16. Chizhov A.Ya., Potievskaya V.I. Intermettent normobaric hypoxia in prevention and treatment of essential hy­pertension. Moscow: Russian University of People's Friendship. 2002.
  17.  
  18. Chowdary S., N. Townend. Role of nitric oxide in the regulation of cardiovascular autonomic control. Clin. Sci. 1999. P. 5-17. CrossRef PubMed
  19.  
  20. Fletcher E.C. Physiological and Genomic Consequences of intermittent hypoxia. Invited review: Physiological consequences of intermittent hypoxia: systemic arterial pressure. JAppl. Physiol. 2001. 90. P. 1600-1605. CrossRef PubMed
  21.  
  22. Foster G.E., Poulin M.J., Hanly P.J. Intermittent hy­poxia and vascular function: implication for obstruc­tive sleep apnoea. Ibid. 2007. 92. P. 51-65. CrossRef PubMed
  23.  
  24. Greenberg H.E., Sica A.L., Scharf S.M., Ruggiero D.A. Expression of c-fos in the rat brainstem after chronic intermittent hypoxia. Brain Res. 1999. 816. P. 638-645. CrossRef  
  25. Hampl V., Comfield D.N., Cowan N.J., Archer S.L. Hypoxia potentiates nitric oxide synthesis and tran­siently increases cytosolic calcium levels in pulmo­nary artery endothelial cells. Eur. Respir. J. 1995. 8. P. 515-522.
  26.  
  27. Hochachka P., Buck L., Doll C, Land S. Unifying theory of hypoxia tolerance: Molecular. metabolic de­fence and rescue mechanisms for surviving oxygen lack. Proc.Natl.Acad.Sci. USA. 1996. 93. P.9493-9498. CrossRef PubMed PubMedCentral
  28.  
  29. Henley W.N., Bellush L.L., Tucker A. Sympatheticand metabolic correlates of hypoxic moderation of spontaneous hypertension in the rat. Proc. Soc. Exp. Biol. Med. 1989. 192, N 2. P. 114-120. CrossRef PubMed
  30.  
  31. Krukoff T.I. Central actions of nitric oxide in regulation of autonomic functions. Brain Res. 1999. 30. P. 52-65. CrossRef  
  32. Lukyanova L.D. Novel approach to the understanding of molecular mechanisms of adaptation to hypoxia. In: Hargens A., Takeda N., Singal P.K., Eds. Adapta­tion Biology and Medicine, v.4 Current Concepts. New Dehli, Narosa, pp 1-19. 2005.
  33.  
  34. Malyshev I.Y., Zenina T.A., Golubeva L.Y. et al. NO-dependent mechanisms of adaptation to hypoxia. Ni­tric Oxide. 1999. 3. P 105-113. CrossRef PubMed
  35.  
  36. Manukhina E.B., Mashina Slu., Smirin B.V. et al. Role of nitric oxide in adaptation to hypoxia and adaptive defense. Phys.Res. 2000. 49. P. 89-97.
  37.  
  38. Manukhina E.B., Downey H.F., Mallet R.T. Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia .Exp.Biol.Med. 2006. 231. P. 343-365. CrossRef PubMed
  39.  
  40. Obrezchikova M.N., Kharchenko I.B., Tarasova O.S., Koshelev V.B. Intermittent hypoxic training in an alti­tude chamber decelerates but not prevents develop­ment of genetically determined hypertension in rats. Hypox. Med. J. 1997. P. 3-7.
  41.  
  42. Paxinos G., Watson C. The Rat Brain in Stereotaxic Coordinates. New York: Acad. Pres. 1982.
  43.  
  44. Scott E., Walker B.R. Increased nitric oxide production following chronic hypoxia contributes to attenuated systemic vasoconstriction. Amer. J.Physiol. Heart Circulat. Physiol. 2003. 284. P. H1655-H1661. CrossRef PubMed
  45.  
  46. Shapoval L.N., Sagach V.F., Pobegailo L.S. Nitric oxide influences ventrolateral medullary mechanisms of va-somotor control in the cat . Neurosci.Lett. 1991. 132. P .47-50. CrossRef  
  47. Shapoval L.N. Nitric oxide and nervous control of car­diovascular function. In: Reseptors, channels and messengers, eds PG.Kostyuk, EA.Lukyanetrz. Kiev: DUS. 2005. P.318-337.
  48.  
  49. Shapoval L.N., Sagach V.F., Pobegailo L.S. Chemosen-sitive ventrolateral medulla in the cat: the fine struc­ture and GABA-induced cardiovascular effects. J.Autonom. Nerv. Syst. 1991. 36. P. 159-172. CrossRef  
  50. Serebrovskaya T.V., Manuchina M.L., Smith H.F., Downey R.T. Mallet. Intermittent Hypoxia: cause of or therapy for systemic hypertension. Minireview. Exp. biol. and med. 2008. 233. P. 627-650. CrossRef PubMed
  51.  
  52. Zanzinger J. Role of nitric oxide in the neural control of cardiovascular functions. Cardiovascul.Res. 1999. 43. P. 839-649. CrossRef  
  53. Zanzinger J., Seller H.. Species differences in the dis­tribution of nitric oxide synthase in brain stem regions that regulate sympathetic activity. Brain Res. 1997. 764. P. 265-268. CrossRef  
  54. Zoccal D.B., Bonagamba L.G.N., Oliveira F.R.T. et al. Increased sympathetic activity in rats submitted to chronic intermittent hypoxia. Exp.Physiol. 2007. 92. P. 79-85. CrossRef PubMed
  55.  
  56. Zong P., Setty S, Sun W. et al. Intermittent hypoxic training protects canine myocardium from infarction. Exp.Biol.Med. 2004. 229. P.806-812. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.