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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(5): 3-12


Role of nitric oxide in the development of the myocardial contractile reactions in trained animals

Shymans'ka TV, Hoshovs'ka IuV, Sahach VF.

    O.O. Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz56.05.003

Abstract

Intensive constitutive production of nitric oxide (NO) during physical training improves vasodilatation and heart function. However, it remains unclear how NO takes part in myocardial adaptation to workload, which is accompanied by an increased heart inflow and intracellular calcium content. Using isolated rat heart by Langendorf preparation, we studied myocardial response to gradually increased left ventricular volume (Frank-Starling low) and increasing concentration of Ca2+ in the perfu-sion solution (from 1.7mM to 12,5 mM) in trained and un­trained rats. It was shown that 4 weeks swimming course improved heart function: heart rate was decreased; contractile activity (dP/dt max) and coronary flow were increased by 20% and 33%, respectively. Equal volume stretching of bal­loon in left ventricle provoked greater contraction in trained comparing to untrained hearts, demonstrating extended func­tional reserves after swimming course. Mitochondrial membrane potential was significantly increased in hearts of trained rats. Furthermore, training prevented fast increase of the end dias-tolic pressure during calcium upload. Mitochondrial factor release due to opening of mitochondrial permeability transi­tion pore (MPTP) in trained hearts was detected at higherconcentrations of calcium that reveals extended calcium capacity of mitochondria and lesser sensitivity of MPTP to its induc­tor – calcium. Blockade of NO synthesis with L-NAME ap­plication of (10-4 M for 15 min) abolished reaction of trained heart during Frank-Starling and calcium upload. Thus, heart adaptation to physical training and extension of functional reserves in heart are provided by endogenous NO production.

Keywords: nitric oxide, Frank-Starling low, physical training,calcium upload, mitochondrial permeability transition,membrane potential

References

  1. Basiluk OV, Kotsyuruba AV, Stepanenko LG, Talanov CO., Korkach YP, Sagach VF Age-specific features of changes in the system of nitric oxide in vessels and plasma under conditions of adaptation to physical activity . Fiziol zh. 2010. 56. N 1. p. 3-12.
  2.  
  3. Kosterin S.A., Bratkova N.F., Kurskii M.D. Rol' sarkolemmi i mitohondrii v obespechenii kal'tsie-vogo kontrolya rasslableniya miometriya . Biohimiya. 1985. 50, N 8. S. 1350-1361.
  4.  
  5. Sagach V.F., Tkachenko M.N., Dmitrieva A.V. O roli endoteliya v reaktsii reaktivnoi giperemii koro­narnih sosudov .Dokl. AN SSSR. 989. 307, N 3. S. 765-767.
  6.  
  7. Sagach VF, Shimanska TV, Nadtochiy SM. The factor released during reperfusion of the ischemic heart may be a marker of mitochondrial pore opening . Fiziol zh. 2003. 49, N 4. p. 6-12.
  8.  
  9. Talanov S.A., Burii V.A., Sagach V.F. Vliyanie adaptatsii k dozirovannim fizicheskim nagruzkam na funktsiyu miokarda kris . Neirofiziologiya. 2009. 41, N 1. S. 41-47.
  10.  
  11. Chorna SV., Talanov SA, Strutinskaya NA, Vavilova GL, Kotziuruba AV, Gaidai MI, Sagach VF The effect of prolonged physical activity on changes in the function of the heart of rats during ischemia-reperfusion, calcium sensitivity of induced mitochondrial pore and the expression of cleavage protein 3 . Fiziol zh. 2010. 56, N 1. P.13-21. CrossRef  
  12. Shimanskaya TV, Dobrovol'skii F.V., Vavilova G.L. N.A.Strutinskaya, E.V.Rudik, Sagach V.F. NO-zavisimaya modulyatsiya chuvstvitel'nosti otkritiya mitohondrial'noi pori pri ishemii-reperfuzii izolirovannogo serdtsa . Ros.fiziol.zhurn. im. I.M. Sechenova. 2009. 95, N 1. S.28-37.
  13.  
  14. Abete P., Calabrese C., Ferrara N., Cioppa A., Pisanelli P., Cacciatore F., Longobardi G., Napoli C, Rengo F. Exercise training restores ischemic preconditioning in the aging heart . J. Amer. Coll. Cardiol. 2000. 36. P.643-650. CrossRef  
  15. Balakirev M., Khramtsov V., Zimmer G. Modulation of the mitochondrial permeability transition by nitric oxide . Eur. J. Biochem. 1997. 246. P. 710-718. CrossRef PubMed
  16.  
  17. Bernstein R.D., Ochoa F.Y., Xu X.B., Forfia P., Shen W., Thompson C.I., Hintze T.H. Function and pro­duction of nitric oxide in the coronary circulation of the conscious dog during exercise. Circulat. Res. 1996. 79. P. 840-848. CrossRef PubMed
  18.  
  19. Borutaite V., Mildaziene V., Brown G.C, Brand M.D. Control and kinetic analysis of ischemia-damaged heart mitochondria: which parts of the oxidative phospho­rylation system are affected by ischemia? . Biochim. Biophys. Acta. 1995. 1272. P. 154-158. CrossRef  
  20. Bowles D.K ., Starnes J.W. Exercise training improves metabolic response after ischemia in isolated working rat heart . J. Appl. Physiol. 1994. 76, issue 4. P.1608-1614. CrossRef PubMed
  21.  
  22. Brand M.D. in Brown G.C, Cooper CE. Editors, Bioenergetics: a practical approach. Oxford.: IRL Press. 1995. P. 39-62.
  23.  
  24. Brookes P., Salinas E., Darley-Usmar K., Eiserich J.P., Freeman B.A., Darley-Usmar V.M., Anderson P.G. Concentration-dependent effect of nitric oxide on mi­tochondrial permeability transition and cytochrom c release . J. Biol. Chem. 2000. 275. P.20474-20479. CrossRef PubMed
  25.  
  26. Dedkova E.N., Blatter L.A. Characteristics and func­tion of cardiac mitochondrial nitric oxide synthase . J. Physiol. 2009. 587, N 4. P.851-872. CrossRef PubMed PubMedCentral
  27.  
  28. Endo T., Imaizumi T., Tagawa T., Shiramoto M., Ando S., Takeshita A. Role of nitric oxide in exercise-induced vasodilation of the forearm . Circulat. 1994. 90. P. 2886-2890. CrossRef PubMed
  29.  
  30. French J.P., Hamilton K.L., Quindry J.C., Lee Y., Upchurch P.A., Powers S.K. Exercise-induced protec­tion against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain . FASEB J. 2008. 22, N 8. P. 2862-2871. CrossRef PubMed PubMedCentral
  31.  
  32. Hoydal M.A., Wisloff U., Kemi O.J., Britton S.L., Koch L.G., Smith G.L., Ellingsen O. Nitric oxide syntase type-1 modulates cardiomyocyte contractility and calcium handling: assotiation with low intrinsic aerobic capacity . Eur. J. Cardiovasc. Prev. Rehabil. 2007. 14. P.319-325. CrossRef  
  33. Hwang H., Reiser P.J., Billman G.E. Effects of exer­cise training on contractile function in myocardial trabe­cule after ischemia-reperfusion. J. Appl. Physiol. 2005. 99,N 1. P.230-236. CrossRef PubMed
  34.  
  35. Quindry J.C, Hamilton K.L., French J.P., Lee Y., Murlasits Z., Tumer N., Powers S.K. Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis. J. Appl. Physiol. 2007. 103. P. 1056-1062. CrossRef PubMed
  36.  
  37. Kavazis A.N., McClung J.M., Hood D.A., Powers S.K. Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli . Amer. J. Physiol. 2008. 294. P. H928-H935. CrossRef PubMed
  38.  
  39. Kemi O.J., Ellingsen O., Smith G.L., Wisloff U. Exer­cise-induced changes in calcium handling in left ven-tricular cardiomyocytes . Front Biosci. 2008. 13. P.356-368. 23.Kingwell B.A. Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease . FASEB J. 2000. 14. P.1685-1696. CrossRef PubMed
  40.  
  41. Le Page C, Noirez P., Counrty J., Riou B., Swynghe-dauw B., Besse S. Exercise training improves func­tional post-ischemic recovery in senescent heart. Exp. Geront. 2009. 44. P.177-182. CrossRef PubMed
  42.  
  43. Maiorana A., O'Driseoll, Tayler R, Green D. Exercise and the nitric oxide vasodilator system . Sports Med. 2003. 33,N 7. P.1013-1035. CrossRef PubMed
  44.  
  45. Marcil M., Bourduas K., Ascah A., Burelle Y. Exercise training induces respiratory substrate-specific decrease in Ca2 induced permeability transition pore opening in heart mitochondria . Amer. J. Physiol. 2006. 290. P. H1549-H1557. CrossRef PubMed
  46.  
  47. Nadtochiy S.M., Tompkins A., Brookes P.S. Different mechanisms of mitochondrial proton leak in ischaemia. reperfusion injury and precondition: implications for pathology and cardioprotection . Biochem. J. 2006. 395. P. 611-618. CrossRef PubMed PubMedCentral
  48.  
  49. Prendergast B.D., Sagach V.F., Shah A.M. Basal release of nitric oxide augments the Frank-Starling response in the isolated heart . Circulation. 1997. 96, N 4. P.1320-1329. CrossRef PubMed
  50.  
  51. Rimbaud S., Garnier A., Ventura-Clapier R. Mitochon­drial biogenesis in cardiac pathology . Pharmacol. Res. 2009. 61. P.131-138. CrossRef  
  52. Roberts C.K., Barnard R.J., Jasman A., Balon T.W. Acute exercise increases nitric oxide synthase activity in skeletal muscle . Amer. J. Physiol. 1999. 277. P. E390-E394. CrossRef PubMed
  53.  
  54. Sagach V.F., Kindybalyuk A.M., Kovalenko T.N. Func­tional hyperemia of skeletal muscle: role of endothe­lium . J.Cardial. Pharmacol. 1992. 20, suppl. 12. P.S170-S175. CrossRef PubMed
  55.  
  56. Shimanskaya T.V Goshovska Y, Sagach V. The role of mitochondrial permeability transition pore in modula­tion of oxygen cost of myocardial work by endogenous NO. In: Advances in Biomedical Research. Cambridge. 2010. P.313-317.
  57.  
  58. Starnes J.W., Barnes B.D., Olsen M.E. Exercise train­ing decreases rat heart mitochondria free radical gen­eration but does not prevent Ca2+-induced dysfunction . J. Appl. Physiol. 2007. 102. P. 1793-1798. CrossRef PubMed
  59.  
  60. Stolen T.O., Hoydal M.A., Kemi O.J., Catalucci D., Ceci M., Aasum E., Larsen T., Rolim N., Condorelli G., Smith G.L., Wislmff U. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of dia­betic cardiomyopathy . Circulat. Res. 2009. 105. P.527-536. CrossRef PubMed
  61.  
  62. Strensberg A. Keller C, Hillig T., Frosig C, Wojtaszew-ski J.F., Pedersen B.K., Pilegaard H., Sander M. Nitric oxide production is a proximal signaling event control­ling exercise-induced mRNA expression in skeletal muscle. FASEB J. 2007. 21, N 11. P.2683-2694. CrossRef PubMed
  63.  
  64. Sun M., Zhang M., Gu J., Qian F.L., Gu J.Z., Chen H. Effects of different levels of exercise volume on endot-helium-dependent vasodilatation: roles of nitric oxide synthase and heme oxygenase . Hypertens Res. 2008. 31, N 5. P. 805-816. CrossRef PubMed
  65.  
  66. Tatchum-Talom R,Schulz R., McNeill J.R., Khadour F.H. Upregulation of neuronal nitric oxide synthase in skeletal muscle by swim training . Amer. J. Physiol. 2000. 279,N 4. P.H1757-H1766. CrossRef PubMed
  67.  
  68. Taylor R.P., Ciccolo J.T., Starnes J.W. Effect of exer­cise training on the ability of the rat heart to tolerate hydrogen peroxide . Cardiovasc. Res. 2003. 58, N 3. P.575-581. CrossRef  
  69. Yamashita N., Hoshida S., Otsu K., Asahi M., Kuzuya T., Hori M. Exercise provides biphasic cardiopro­tection via manganese superoxide dismutase activation . J. Exp. Med. 1999. 189. P. 1699-1706. CrossRef PubMed PubMedCentral

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