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. 2013; 59(4): 16-27


Biochemical mechanisms of the cardioprotective effect of the K(ATP) channels opener flocalin (medicinal form) in ischemia-reperfusion of myocardium

Strutyns'kyĭ RB1, Kotsiuruba AV1, Rovenets' RA1, Strutyns'ka NA1, Iagupols'kyĭ IuL2, Sagach VF1, Moĭbenko OO1

  1. O.O.Bogomoletz Institute of Physiology National Academyof Science of Ukraine, Kyiv, Ukraine
  2. Institute of Organic Chemistry National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz59.04.016

Abstract

In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min) of myocardium it was investigated changes of biochemical processes in arterial blood at intragastric introduction of medicinal form (tablets) of flocalin (the fluorine-containing opener of ATP-sensitive potassium channels) in a dose 2,2 mg/kg. The data analysis allowed to define a few possible mechanisms of cardioprotective action offlocalin, which prevented the opening of a mitochondrial permeability transition pore (MPTP) and inhibition of apoptosis induced by it. They consist, from one side, in activating of the constitutive de novo biosynthesis of nitric oxide by cNOS, from other side, in suppression of inducible nitric oxide de novo synthesis by iNOS in such way to prevent the formation of toxic peroxynitrite by co-operation of surplus nitric oxide with superoxide anion, thereby limits the generation of toxic active forms of nitrogen (*NO2) and oxygen (*OH). The first effect of flocalin takes place due to limitation the degradation of L-arginine by arginase which keeps substrat for cNOS, second--due to the inhibition of superoxide generation, in particular, by xanthine oxidase (marker uric acid), lipoxigenase (marker LTC4) and cyclooxygenase (marker TxB2). Because LTC4 have coronaroconstrictory, arrhythmogenic and chemoattractory properties in the conditions of myocardial ischemia, inhibition of its production both with superoxide generation (markers H2O2 and diene conjugates) may be the another mechanisms of flocalin's cardioprotection. Powerful antiischemic action of flocalin (marker nitrite anion) as the mechanisms of cardioprotection is possible as well as inhibition of ATP and GTP degradation (marker hypoxanthine+xanthine+inosine levels in the blood) and, possibly, stimulation ofhaem degradation by haem oxygenase (markers total bilirubin and Fe in the blood). Diminishing content of free arachidonic acid in arterial blood can testify inhibition of cellular membranes phospholipides degradation by phospholipase A2 as a result of flocalin cardioprotection.

Keywords: KATP-channels, flocalin, ischemia-reperfusion, oxidative stress, nitrozative stress, lipid peroxidation , de novo synthesis of NO, arginase

References

  1. Gavrilov V.B., Gavrilova A.R., Hmara N.F. Izmerenie dienovih kon'yugatov v plazme krovi po UF-pogloshcheniyu geptanovih i izopropanol'nih ekstraktov . Lab. delo. 1988. N 2. P. 60-64. PubMed
  2.  
  3. Moibenko O.O., Strutins'kii R.B., Yagupol's'kii L.M., Mohort M.A. Rozrobka ta pidgotovka do vprovadzhennya novogo vitchiznyanogo kardioprotektornogo preparatu ftorvmisnogo aktivatora ATF-zalezhnih kaliievih kanaliv Flokalin . Nauka ta innovatsii. 2006. 2, N 4. P. 77-82.
  4.  
  5. Pokrovskii A.A. Biohimicheskie metodi issledovaniya v klinike. M.: Meditsina, 1969. 437 p.
  6.  
  7. Strutins'kii R.B., Kotsyuruba A.V., Neshcheret O.P., Rovenets' R.A., Moibenko O.O. Zmini metabolizmu v miokardi pri ishemii-reperfuzii ta aktivatsii adenozintrifosfatchutlivih kaliievih kaliievih kanaliv . Fiziol. zhurn. 2012. 58, N 1. P. 13-26.
  8.  
  9. Strutins'kii R.B., Pivovar S.M., Tumanovs'ka L.V., Moibenko O.O. Kardioprotektorni efekti flokalinu: vidnosna rol' aktivatsii sarkolemal'nih ta mitohondrial'nih adenozintrifosfatzalezhnih kaliievih KATF kanaliv . Tam samo. 2008. 54, N 6. P.15-23.
  10.  
  11. Strutins'kii R.B., Rovenets' R.A., Strutins'ka N.A., Neshcheret O.P., Moibenko O.O. Vpliv aktivatsii adenozintrifosfatchutlivih kaliievih kanaliv flokalinom na funktsiyu sertsevo-sudinnoi sistemi . Tam samo. 2013. 59, N 1. P. 11-16.
  12.  
  13. Strutins'kii R.B., Rovenets' R.A., Neshcheret O.P., Tumanovs'ka L.V., Boichuk T.M., Dzhuran B.V., Moibenko O.O. Vpliv likars'koi formi flokalinu na perebig ishemii-reperfuzii miokarda . Tam samo. 2011. 57, N 1. P. 55-65.
  14.  
  15. Shugalei V.S., Kozina A.S. Soderzhanie mochevini i aktivnost' arginazi v organah kris pri aklimatizatsii k holodu . Fiziol. zhurn. SSSR. 1977. N 8. P.1199-1202.
  16.  
  17. Boyde T.R., Rahmatullah M. Optimization of conditions for the colorimetric determination of citrulline, using diacetul monoxime . Anal. Biochem. 1980. 107, N 2. P. 424-431. CrossRef  
  18. Chin S.Y., Pandey K.N., Shi S.J. Increased activity and expression of Ca2+-dependent NOS in renal cortex of ANG II-infused hypertensive rats . Amer. J. Physiol. 1999. 277, N 5. P. 797-804.
  19.  
  20. Conte D., Narindrasorasa K. S., Sarkar B. In vivo and in vitro iron replaced zinc finger generates free radicals and causes DNA damage . Eur. J. Biochem. 1996. 271, N 9. P.5125-5130.
  21.  
  22. Green L.L., Wagner D.A., Glogowski J. Analysis of nitrate, nitrite and [+5N] nitrate in biological fluids . Anal. Biochem. 1982. 126, N 1. P.131-138. CrossRef  
  23. Gross G.J., Fryer R.M. Sarcolemmal versus mitochondrial ATP-sensitive K+ channels and myocardial preconditioning . Circ. Res. 1999. 84, N 9. P. 973-979. CrossRef PubMed
  24.  
  25. Halestrap A.P., Clarke S.J., Javadov S.A. Mitochondrial permeability transition pore opening during myocardial reperfusion a target for cardioprotection . Cardiovasc. Res. 2004. 61. P. 372-385. CrossRef  
  26. Hanley P.J., Daut J. K(ATP) channels and preconditioning: a re-examination of the role of mitochondrial K(ATP) channels and an overview of alternative mechanisms . J. Mol. Cell. Cardiol. 2005. 1.P.17-50. CrossRef PubMed
  27.  
  28. Salter M., Knowles R.G., Moncada S. Widespread tissue distribution, species and changes in activity of Ca2+dependent and Ca2+-independent nitric oxide syntases . FEBS Lett. 1991. 291, N 1. P. 145-149. CrossRef  
  29. Strutynskyi R.B., Kotsuruba A.V., Neshcheret A.P., Shysh A.N., Rovenets R.A., Moibenko A.A Cardioprotective Effects of ATP-Sensitive Potassium Channels Activation in Experiments in Vivo: Influence on Biochemical Parameters of Blood Following Ischemia-Reperfusion of Myocardium . Int. J. Phys. Pathophys. 2010. 1, N 4. P.305-313. CrossRef  
  30. Strutynskyi R.B., Neshcheret A.P., Tumanovska L.V., Rovenets R.A., Moibenko A.A. Cardioprotective effects of flocalin in in vivo experiments: influence of the hemodynamic and on the damage of myocardium under ischemia-reperfusion . Ibid. 2010. 1, N 3. S. 211-218. CrossRef  
  31. Takase B, Maruyama T, Kurita A, Uehata A, Nishioka T, Mizuno K, Nakamura H, Katsura K, Kanda Y Arachidonic acid metabolites in acute myocardial infarction . Angiology. 1996. 47, N 7. R.649-661.
  32.  
  33. Voitychuk O.I., Strutynskyi R.B., Moibenko O.O., Shuba Y.M. Effects of fluorine-containing opener of ATPsensitive potassium channels, pinacidil-derivative flocalin, on cardiac voltage-gated sodium and calcium channels . NSAP. 2012. 385. N 11. P.1095-1102. CrossRef PubMed
  34.  
  35. Yokoshiki H., Sunagawa M., Seki T., Sperelakis N. ATPsensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells. . Am. J. Physiol. Cell. Physiol. 1998.274.P. 25-37.
  36.  

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