Application of native NO-donor in cardiology

Kapelko V.I.; Lakomkin V.L.; Timoshin A.A.; Rodnenkov O.V.; Zorin A.V.; Abramov A.A.; Lukoshkova E.V.; Ermishkin V.V.; Gramovich V.V.; Vyborov O.N.; Dragnev A.G.; Arzamastsev E.V.; Vanin A.F.

doi:https://doi.org/10.17116/Cardiobulletin20191402126

Kapelko V.I.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Lakomkin V.L.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Timoshin A.A.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Rodnenkov O.V.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Zorin A.V.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Abramov A.A.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Lukoshkova E.V.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Ermishkin V.V.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Gramovich V.V.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Vyborov O.N.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Dragnev A.G.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Arzamastsev E.V.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Vanin A.F.

Semenov institute of chemical physics of the Russian academy of sciences, Moscow, Russia;
Institute for regenerative medicine, Sechenov First Moscow State Medical University, Moscow, Russia

Application of native NO-donor in cardiology

Authors:

Kapelko V.I., Lakomkin V.L., Timoshin A.A., Rodnenkov O.V., Zorin A.V., Abramov A.A., Lukoshkova E.V., Ermishkin V.V., Gramovich V.V., Vyborov O.N., Dragnev A.G., Arzamastsev E.V., Vanin A.F.

More about the authors

Journal: Russian Cardiology Bulletin. 2019;14(2): 26‑35

DOI: 10.17116/Cardiobulletin20191402126

Read: 2516 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Kapelko VI, Lakomkin VL, Timoshin AA, et al. . Application of native NO-donor in cardiology. Russian Cardiology Bulletin. 2019;14(2):26‑35. (In Russ.)
https://doi.org/10.17116/Cardiobulletin20191402126

Подписка 2026 Кардиологический вестник (Russian Cardiology Bulletin)

Использование инфографики авторами научных работ

Close metadata

Recommended articles:

Influence of enzymatic activity of microbiota on hemodynamics, arterial stiffness and emotional state of patients with mild-to-moderate risk of cardiovascular complications. Russian Cardiology Bulletin. 2024;(4-2):128-136

Laboratory biomarkers for the prognosis of chronic heart failure. Laboratory Service. 2024;(3):5-16

Resolution of the expert council «Possibilities of neuroprotective therapy in patients with arterial hypertension and cognitive disorders». Russian Journal of Preventive Medicine. 2024;(11):85-93

The significance of exogenous nitrate and nitrite of plant origin for vascular health. Russian Journal of Preventive Medicine. 2024;(11):141-146

Diaphragm dysfunction as a prognostic criterion of external respiratory impairment and necessary extracorporeal membrane oxygenation in patients with chronic heart failure. Russian Journal of Anesthesiology and Reanimatology. 2024;(6):38-45

The potentials of the six-minute walking test in clinical practice automatization and advanced features. Russian Journal of Preventive Medicine. 2024;(12):122-127

The role of quantitative body composition analysis in population in the assessment and monitoring of cardiovascular risk metabolic factors. Russian Journal of Preventive Medicine. 2024;(12):128-134

Cuffless methods of blood pressure measurements. Review of modern technologies. Russian Journal of Preventive Medicine. 2024;(12):156-162

Modern aspects of chronic cerebral ischemia pathogenetic therapy. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(12):106-113

Biomarkers of atherothrombotic and cardioembolic subtypes of acute ischemic stroke. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(12-2):20-26

Abstract:

The experimental and clinical data of usage of stable nitric oxide donor, dinitrosyl iron complexes, are considered. On the basis of this compound, the drug Oxacom was created in the National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, Its hypotensive effect, unlike other nitric oxide donors, was much more prolonged — up to 8—10 hours in humans due to gradual release of nitric oxide from complexes. The drug successfully passed two phases of clinical trials. Oxacom also had ability to reduce the pressure in a small circle of rats with pulmonary hypertension. The drug reduced coronary tone in the isolated rat heart, and in vivo experiments increased myocardial contractility and relaxabiity in rats with CHF. This ability makes Oxacom a promising drug for the treatment of cardiac pathologies with reduced myocardial NO-synthase activity.

Keywords:

nitric oxide

dinitrosyl iron complexes

arterial hypertension

pulmonary hypertension

chronic heart failure

Authors:

Kapelko V.I.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Lakomkin V.L.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Timoshin A.A.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Rodnenkov O.V.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Zorin A.V.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Abramov A.A.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Lukoshkova E.V.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Ermishkin V.V.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Gramovich V.V.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Vyborov O.N.

National Cardiology Research Center, Russian Ministry of Health, 3 Cherepkovskaya 15A, Moscow, 121552, Russian Federation

Dragnev A.G.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Arzamastsev E.V.

Federal State budget organization «National medical research center of cardiology» of the Ministry of healthcare of the Russian Federation, Moscow, Russia

Vanin A.F.

Semenov institute of chemical physics of the Russian academy of sciences, Moscow, Russia;
Institute for regenerative medicine, Sechenov First Moscow State Medical University, Moscow, Russia

Close metadata

References:

Kleshchev AL, Mordvintcev PI, Vanin AF. Role of nitric oxide and iron in hypotensive action of nitrosyl iron complexes with various anionic ligands. Studia Biophys. 1985;105:93-102. (In Russ.)
Trochu J-N, Bouhour J-B, Kaley G, Hintze TH. Role of Endothelium-Derived Nitric Oxide in the Regulation of Cardiac Oxygen Metabolism: Implications in Health and Disease. Circ Res. 2000;87:1108-1117.
Marcov HM. Molecular mechanisms of vascular endothelium dysfunction. Kardiologiia. 2005;12:62-72. (In Russ.) ISSN: 0022-9040.
Aronov DM, Lupanov VP. Nitrates in complex angina management during the age of aggressive coronary atherosclerosis treatment. Cardiovascular therapy and prevention. 2005;4(5):71-78. (In Russ.) ISSN: 1728-8800.
Zhirov IV, Tereshchenko SN. Intravenous nitrates in modern cardiology. Cardiovascular therapy and prevention. 2005;4(6-1):97-101. (In Russ.) ISSN: 1728-8800.
Serdechno-sosudistaia patologiya. Sovremennoe sostoyanie problemi. Pod red. Eliseeva O.M. M.: Izdatel’stvo Media Medica; 2009. (In Russ.) ISBN: 978-5-903574-09-4.
Daiber A, Oelze M, Coldewey M, et al. Oxidative stress and mitochondrial aldehyde dehydrogenase activity: a comparison of pentaerythritol tetranitrate with other organic nitrates. Mol Pharmacol. 2004;66:1372-1382.
Vedernikov YP, Mordvintcev PI, Malenkova IV, Vanin AF. Similarity between the vasorelaxing activity of dinitrosyl iron cysteine complexes and endothelium-derived relaxing factor. Eur J Pharmacol. 1992;211(3):313-317. https://doi.org/10.1016/0014-2999(92)90386-I
Vanin AF. Dinitrosyl-iron complexes with thiolate ligands: Physico-chemistry, biochemistry and physiology (Review). Nitric Oxide Biol & Chem. 2009;21:136-149. https://doi.org/10.1016/j.niox.2009.03.005
Vanin AF, Chazov EI. Prospects of designing medicines with diverse therapeutic activity on the basis of dinitrosyl iron complexes with thiol-containing ligands. Biophysics. 2011;56(2):304-315. (In Russ.) https://doi.org/10.1134/S0006350911020321
Lakomkin VL, Vanin AF, Timoshin AA, Kapelko VI, Chazov EI. Long-lasting hypotensive action of stable preparations of dinitrosyl iron complexes with thiol-containing ligands in conscious normotensive and hypertensive rats. Nitric Oxide. 2007;16(4):413-418. https://doi.org/10.1016/j.niox.2007.03.002
Lakomkin VL, Timoshin AA, Orlova TsR, Gubkina SA, Storozhilova AN, Gvozdik TE, Dobrovolsky AB, Ruuge EK, Vanin AF, Kapelko VI, Lapin BA, Chazov EI. Action of a Nitric Oxide Donor Dinitrosyl Complex of Iron With Glutathione on the Circulation in Rats and Monkeys. Kardiologiya. 2009;49(5):53-60. (In Russ.) ISSN: 0022-9040.
Timoshin AA, Lakomkin VL, Abramov AA, Ruuge EK, Kapel’ko VI, Chazov EI, Vanin AF. The hypotensive effect of the nitric monoxide donor Oxacom at different routs of its administration to experimental animals. Eur J Pharmacol. 2015;765:525-532. https://doi.org/10.1016/j.ejphar.2015.09.011
Chazov EI, Rodnenkov OV, Zorin AV, Lakomkin VL, Gramovich VV, Vyborov ON, Dragnev AG, Timoshin AA, Buryachkovskaya LI, Abramov AA, Masenko VP, Arzamastsev EV, Kapelko VI, Vanin AF. Hypotensive effect of «oxacom» containing a dinitrosyl iron complex with glutathione: animal studies and clinical trials in healthy volunteers. Nitric Oxide. 2012;26(3):148-156. https://doi.org/10.1016/j.niox.2012.01.008
Paulus WJ, Bronzwaer JG. Myocardial contractile effects of nitric oxide. Heart Fail Rev. 2002;7(4):371-383.
Massion PB, Feron O, Dessy C, Balligand J-L. Nitric Oxide and Cardiac Function: Ten Years After, and Continuing. Circ Res. 2003;93:388-398.
Gosteev AYu, Zorin AV, Rodnenkov OV, Dragnev AG, Chazov EI. Hemodynamic effects of the synthetic analogue of endogenous nitric oxide (II) donors a dinitrosyl iron complex in hypertensive patients with uncomplicated hypertensive crisis. Terapevticheskiy arkhiv (Therapeutic archive). 2014;86(9):49-55. (In Russ.) ISSN: 0040-3660.
Lakomkin VL, Abramov AA, Lukoshkova EV, Ermishkin VV, Kapelko VI. The influence of the nitric oxide donor on cardiac contractile properties ex vivo and in vivo. Rossiiskii fiziologicheskii zhurnal im. I.M. Sechenova. Rossiiskaia akademiia nauk. 2017;103(1):71-78. (In Russ.) ISSN: 0869-8139.
Lakomkin VL, Abramov AA, Lukoshkova EV, Ermishkin VV, Kapelko VI. Cardiotropic Action of Oxacom in Experimental Heart Failure. Kardiologiya. 2015;55(1):37-42. (In Russ.) ISSN: 0022-9040.
Lakomkin VL, Orlova TcR, Abramov AA, Sviriaeva IV, Shumaev KB, Ruuge EK, Vanin AF, Kapelko VI. Chronotropic regulation of the heart at hypotensive effect induced reactive oxygen species. Russian Cardiology Bulletin («Kardiologicheskij Vestnik»). 2011;6(1):53-59. (In Russ.) ISSN: 2077-6764.
Pinsky DJ, Patton S, Mesaros S, Brovkovych V, Kubaszewski E, Grunfeld S, Malinski T. Mechanical transduction of nitric oxide synthesis in the beating heart. Circ Res. 1997;81(3):372-379.
Poteser M, Romanin C, Schreibmayer W, Mayer B, Groschner K. S-nitrosation controls gating and conductance of the alpha 1 subunit of class C L-type Ca(2+) channels. J Biol Chem. 2001;276:14797-14803. https://doi.org/10.1074/jbc.M008244200
Filice E1, Angelone T, De Francesco EM, Pellegrino D, Maggiolini M, Cerra MC. Crucial role of phospholamban phosphorylation and S-nitrosylation in the negative lusitropism induced by 17β-estradiol in the male rat heart. Cell Physiol Biochem. 2011;28(1):41-52. https://doi.org/10.1159/000331712
Salama G, Menshikova EV, Abramson JJ. Molecular interaction between nitric oxide and ryanodine receptors of skeletal and cardiac sarcoplasmic reticulum. Antioxid Redox Signal. 2000;2(1):5-16. https://doi.org/10.1089/ars.2000.2.1-5
Xu L, Eu JP, Meissner G, Stamler JS. Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science. 1998;279:234-237. https://doi.org/10.1126/science.279.5348.234
Timoshin AA, Lakomkin VL, Ruuge EK, Vanin AF. Distribution and pharmacokinetics of dinitrosyl iron complexes in rat organs. Biophysics. 2012;57(2):331-337. (In Russ.) ISSN: 0006-3029.
Abramov AA, Lakomkin VL, Timoshin AA, Lukoshkova EV, Ermishkin VV, Kapelko VI. Effect of oxacom on the right ventricular pressure in rats with monocrotalin-induced pulmonary. Arterial hypertension. 2017;23(5):412-420. (In Russ.) https://doi.org/10.18705/1607-419X-2017-23-5-412-420
Zhang YH, Jin CZ, Jang JH, Wang Y. Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. J Physiol. 2014. https://doi.org/10.1113/jphysiol.2013.270306
Lima B, Forrester MT, Hess DT, Stamler JS. S-nitrosylation in cardiovascular signaling. Circ Res. 2010;106:633-646. https://doi.org/10.1161/CIRCRESAHA.109.207381
Silberman GA, Fan TH, Liu H, et al. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation. 2010;121(4):519-28. https://doi.org/10.1161/CIRCULATIONAHA.109.883777
Gonzalez DR, Beigi F, Treuer AV, Hare JM. Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes. Proc Natl Acad Sci USA. 2007;104:20612-100617. https://doi.org/10.1161/CIRCULATIONAHA.109.883777
Rassaf T, Poll LW, Brouzos P, et al. Positive effects of nitric oxide on left ventricular function in humans. European Heart Journal. 2006;27:1699-1705.