The changes of metabolism in myocardium at ischemia-reperfusion and activating of the ATP-sensitive potassium channels
Strutyns'kyĭ RB, Kotsiuruba AV, Neshcheret OP, Rovenets' RA, Moĭbenko OO.
O.O.Bogomoletz Institute of Physiology National Academy of Science of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz58.01.013
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Abstract
In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min) it was investigated the changes of biochemical processes in the different areas of heart ( intact, risk and necrotic zone) during 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 cardioprotective mechanisms of flocalin action at ischemia-reperfusion conditions: the preservation of sufficient levels of de novo (by cNOS) NO synthesis, an inhibition of de novo (by iNOS) and salvage (by NADH-depen-dent nitratreductase) NO synthesis, an inhibition of L-arginine degradation by arginase, an inhibition of oxidizing metabolism due to limitation of ROS and RNS generation, inhibition of free arachidonic acid and eicosanoids synthesis, inhibition of AT P and GTP degradations and, possibly, stimulation of protective haem degradation. These changes may prevent formation of toxic peroxynitrite and suggest the possibility of participating in flocalin–mediated cardioprotective effects of warning a mitochondrial permeability transition pore (MPTP) opening and inhibition of apoptosis and/or necrosis of cardiomyo-cytes induced by it.
Keywords:
аденозинтрифосфатчувствительныекалиевые каналы, флокалин, ишемия–реперфузия,оксидативный стресс, нитрозативный стресс, перекисноеокисление липидов, de novo синтез NO, реутилизационныйсинтез NO.
References
- Gavrilov V.B., Gavrilova A.R., Khmara N.F. Measurement of diene conjugates in blood plasma by UV absorption of heptane and isopropanol extracts . Lab. a business. 1988. No. 2. S. 60-64.
- Moibenko O.O., Strutinsky RB, Yagupolsky Yu.L., Voytichuk O.I., Shuba Ya.M. Possible mechanisms of cardioprotective effects of activation of the Kdta channels in case of myocardial ischemia reperfusion . Bull. XX-chit im. V.V. Shdvisotsky (26-27 herbs. 2011). Odessa, 2011 . S. 135-136.
- Moibenko O.O., Strutinsky RB, Yagupolsky L.M., Mohort M.A., Shalamay A.S. Organization of factory preparation for Flocalin drug, a new vyschiznyny myotropic antispasmodic and cardioprotector . Science and Innovation. 2009. 5, No. 1. C 80-84.
CrossRef
- Pokrovsky A.A. Biochemical research methods in the clinic M .: Medicine, 1969. 437 p.
- Steel I.D., Garishvili T.G. Method for determination of malondialdehyde using thiobarbituric acid. In the book: Sovr. Methods in Biochemistry . Ed. Orekhovich V.N. M .: Medicine, 1977 .-- S. 66-67.
- Strutinsky R.B., Pivovar S.N., Moibenko A.A. ATP-dependent potassium channels and their role as the central link of cardioprotection in ischemia myocardial reperfusion. In the book: Endogenous mechanisms of cardioprotection as the basis of the pathogenetic therapy of heart diseases. K .: Science. Dumka, 2008 .-- S. 206-252.
- Strutinsky R.B., Brewer SM., Tumanovska L.V., Moibenko O.O. Cardioprotective effects of flocalin: the role of activation of sarcolemal and mitochondrial adenosine triphosphate fallow caldium channel is clear . Fiziol.zhurn. 2008. 54, No. 6. S 15-23.
- Strutinsky R.B., Rovenets R.A., Nescheret O.P., Tumanovska L.V., Boychuk T.M., Juran B.V., Moibenko O.O. Influence of the likarskoi form of flocalin on the rebound of ischemia reperfusion of the myocardium . There Itself. 2011. 57, No. 1. C 55-65.
- Shugaley B.C., Kozina A.S. Urea content and arginase activity in rat organs during acclimatization to cold . Fiziol. journal THE USSR. 1977, No. 8. FROM. 1199-1202
- Boyde T.R., Rahmatullah M. Optimization of conditions for the colorimetric determination of citrulline, using diacetyl monoxime . Anal. Biochem. 1980. 107, N 2. P. 424-431.
CrossRef
- 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.
CrossRef
PubMed PubMedCentral
- Coceani F. Carbon monoxide in vasoregulation: The promise and the challenge . Circulat. Res. 2000. 86, N 12. P. 1184-1186.
CrossRef
PubMed
- 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.
CrossRef
PubMed
- Das A, Smolenski A, Lohmann SM, Kukreja RC. Cyclic GMP-dependent protein kinase 1alpha attenuates necrosis and apoptosis following ischemia. reoxygen-ation in adult cardiomyocyte . J. Biol. Chem. 2006. 281, N 50. P. 38644-38652.
CrossRef
PubMed
- 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
- Gerdel D., Cederbaum A.J. Inhibition of the catalitic activity of alkoholdegydrogenase by NO is associated with S-nitrosylation and the release of zinc . Biochemistry. 1996. 35, N 50. P. 16186-16194.
CrossRef
PubMed
- Inoue I., Nagase H., Kishi K., Higuti T. ATP-sensitive K+ channels in the mitochondrial inner membrane . Nature. 1991. 352, N 6332. P. 244-247.
CrossRef
PubMed
- Noma A. ATP-regulated K+ channels in cardiac muscle . Ibid. 1983. 305, N 5930. P. 147-148.
CrossRef
PubMed
- 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
- 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. Physiol. Pathophysiol. 2010. 1, N 4. P. 305-313.
CrossRef
- 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. N 3. S 211-218.
CrossRef
- Voitychuk O.I., Strutynskyi R.B., Yagupolskii L.M., Tinker A., Moibenko O.O., Shuba Y.M. Sarcolemmal cardiac KATP channels as a target for the cardioprotective effects of the fluorine-containing pinacidil analogue flocalin . Brit. J. Pharmacol. 2011.- 162, N 3. P. 701-711.
CrossRef
PubMed PubMedCentral
- West M., Rokosh G., Clark D. Nitric oxide prevent mitochondrial permeability transition during ischemic-reperfusion: implication for the cardioprotective effects of late preconditioning . Circulation. 2004. 110. P.III236.
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