MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector39897710.17816/morph.398977ArticlesСтатьиSIGNIFICANCE OF NEURONAL, ENDOTHELIAL AND INDUCIBLE NO-SYNTHASE ISOFORMS IN CARDIAC MUSCLE HISTOPHYSIOLOGYЗНАЧЕНИЕ НЕЙРОНАЛЬНОЙ, ЭНДОТЕЛИАЛЬНОЙ И ИНДУЦИБЕЛЬНОЙ ИЗОФОРМ NO-СИНТАЗ В ГИСТОФИЗИОЛОГИИ СЕРДЕЧНОЙ МЫШЦЫOkhotinV EОхотинВ Е

Лаборатории нейроморфологии с группой электронной микроскопии (руков. - проф. В.Н. Швалев); Российский кардиологический научно-производственный комплекс МЗ РФ и нейрогенетики и генетики развития(зав. - чл.-кор. РАН Л.И. Корочкин) Института биологии гена РАН

ShuklinA VШуклинА В

Лаборатории нейроморфологии с группой электронной микроскопии (руков. - проф. В.Н. Швалев); Российский кардиологический научно-производственный комплекс МЗ РФ и нейрогенетики и генетики развития(зав. - чл.-кор. РАН Л.И. Корочкин) Института биологии гена РАН

OkhotinV E

; Russian Cardiologic Scientific Complex and Laboratory of Neurogenetics and Developmental Genetics, RAS Institute of Gene

ShuklinA V

; Russian Cardiologic Scientific Complex and Laboratory of Neurogenetics and Developmental Genetics, RAS Institute of Gene

Российский кардиологический научно-производственный комплекс МЗ РФ и нейрогенетики и генетики развития(зав. - чл.-кор. РАН Л.И. Корочкин) Института биологии гена РАНRussian Cardiologic Scientific Complex and Laboratory of Neurogenetics and Developmental Genetics, RAS Institute of Gene150320061291NO1 (2006)№1 (2006)71709052023Copyright ©; 2006, Eco-VectorCopyright ©; 2006, Эко-Вектор2006Eco-VectorЭко-Векторhttps://j-morphology.com/1026-3543/article/view/398977

This review summarizes the information on the interrelations between intracellular localization of NO-synthases (NOS) and their regulatory functions within different compartments of a cardiomyocyte in the light of general conception of Barouch et al. (2002) on the intracellular «spatial compartmentalization» of NOS isoforms. Participation of NO in cardiomyocyte function control is based on complex spatial compartmentalization of NOS isoforms: neuronal (NOS1), inducible (NOS2) and endothelial (NOS3), which possess unequal activities resulting in hundredfold differences in the concentrations of gas produced. Regulatory role of constititive Ca-dependent NOS1 and NOS3 is associated with production of low NO concentrations, which cause a decline in cardiomyocyte contractility and a reduction in heart rate. Conversely, Ca-independent inducible NOS2 appears only in the damaged myocardium with a compromised contractile function. NOS2 produces high unregulated NO concentrations, which are connected with the generation of peroxynitrites and NO cytotoxic action. NOS3 is associated with the membranes of cardiomyocyte caveoli and T-tubules, while NOS1 is localized on the sarcoplasmic reticulum membranes. NOS isoform compartmentalization promotes regulation of different circuits in NO-signaling pathways in myocardium, and this principle is a key for understanding of contradictions existing in NO biology in the heart. Changes in NOS subcellular compartmentalization lead to the increased NO synthesis, reduction of the specificity of its effects, disruption of calcium cycle mechanisms, electromechanical uncoupling and myocardial contractility failure. The mechanisms of selective effects of different NO-ergic regulatory pathways on the activity of five major targets in pacemaker and working cardiomyocytes, are discussed.

Обзор обобщает данные о совокупности взаимоотношений между внутриклеточной локализацией NO-синтаз (NOS) и их регуляторными функциями в различных регионах отдельного кардиомиоцита в свете общей концепции L.Barouch и соавт. (2002), о внутриклеточной «пространственной компартментализации» изоформ NOS. В основе участия NO в деятельности кардиомиоцитов лежит сложная пространственная компартментализация NOS: нейрональной (NOS1), индуцибельной (NOS2) и эндотелиальной (NOS3), функция которых в сотни раз различается концентрациями вырабатываемого газа. Регуляторная роль конститутивных кальций-зависимых NOS1 и NOS3 связана с выработкой низких концентраций NO, которые вызывают ослабление сократимости кардиомиоцитов и снижение частоты сердечных сокращений. Напротив, кальций-независимая индуцибельная NOS2 появляется только в поврежденном миокарде с нарушенной сократительной функцией. NOS2 продуцирует высокие нерегулируемые концентрации NO, с которыми связана генерация пероксинитритов и цитотоксическое его действие. NOS3 ассоциирована с мембраной кавеол и Т-трубочек кардиомиоцита, в то время как NOS1 локализована на внутриклеточных мембранах саркоплазматической сети. Компартментализация изоформ NOS обеспечивает регуляцию различных звеньев NO-ергических сигнальных путей в миокарде, и этот принцип является ключевым в понимании противоречий, существующих в биологии NO в сердце. Изменения субклеточной компартментализации NOS ведут к повышению синтеза NO, снижению специфичности его влияния, расстройству механизмов кальциевого цикла, разобщению электромеханического сопряжения и нарушению сократимости миокарда. Обсуждаются механизмы избирательного действия различных NO-ергических регуляторных путей на активность пяти основных мишеней в пейсмейкерных и рабочих кардиомиоцитах.

NOS1NOS2NOS3NOS1NOS2NOS3cardiomyocytessubcellular compartmentalizationкардиомиоцитысубклеточная компартментализацияАлипов Н.Н. Пейсмейкерные клетки сердца: электрическая активность и влияние вегетативных нейромедиаторов. Успехи физиол. наук, 1993, т. 24, № 2, с. 37-69.Ванин А.Ф. Оксид азота в истории биологии: история, состояние, перспективы исследования. Биохимия, 1998, т. 63, № 7, с. 867-869.Ванин А.Ф. Динитрозильные комплексы и S-нитрозотиолы - две возможные формы стабилизации и транспорта оксида азота в биосистемах. Биохимия, 1998, т. 63, № 7, с. 924-938.Горрен А.К. и Майер Б. Универсальная и комплексная энзимология синтазы оксида азота. Биохимия, 1998, т. 63, № 7, с. 870-880.Капелько В.И. Регуляторная роль кислородных радикалов в миокардиальных клетках. Росс. физиол. журн., 2004, т. 90, № 6, с. 681-692.Мазур Н.А. Дисфункция эндотелия, монооксид азота и ишемическая болезнь сердца. Тер. арх., 2003, т. 73, № 3, с. 84-86.Марков Х.М. Оксид азота и сердечно-сосудистая система. Успехи физиол. наук, 2001, т. 32, № 3, с. 49-65.Охотин В.Е., Калиниченко С.Г. и Дудина Ю.В. NO-ергическая трансмиссия и NO как объемный нейропередатчик. Влияние NO на механизмы синаптической пластичности и эпилептогенез. Успехи физиол. наук, 2002, т. 33, № 2, с. 41-55.Охотин В.Е. и Куприянов В.В. Нейровазальные отношения в новой коре головного мозга человека. Морфология, 1996, т. 110, вып. 4, с. 17-22.Реутов В.П., Сорокина Е.Г., Косицин Н.С. и Охотин В.Е. Проблема оксида азота в биологии и медицине и принцип цикличности: ретроспективный анализ идей принципов и концепций. М., Едиториал УРСС, 2003.Реутов В.П., Сорокина Е.Г., Охотин В.Е. и Косицин Н.С. Циклические превращения оксида азота в организме млекопитающих. М., Наука, 1997.Розенштраух Л.В., Сакс В.А., Юриавичус И.А. и др. Влияние креатинфосфата на медленные входящие кальциевые токи, потенциалы действия и силу сокращений предсердий и желудочков лягушки. Биохим. мед., 1979, т. 21, № 1, с. 1-15.Стокле Ж.-К., Мюлле Б., Андрианцитохайна Г. и Клещев А. Гиперпродукция оксида азота в патофизиологии кровеносных сосудов. Биохимия, 1998, т. 63, № 7, с. 976-983.Тищенко О.В., Елисеева Е.В. и Мотавкин П.А. Значение оксида азота в развитии гипертрофии сердца в условиях экспериментальной почечной гипертензии. Цитология, 2002, т. 44, № 3, с. 263-269.Чазов Е.И. Вклад нарушений регуляторных механизмов в развитие сердечно-сосудистых патологий. Тер. арх., 1999, т. 71, № 9, с. 8-12.Шуклин А.В., Реутов В.П. и Охотин В.Е. Регуляторная роль оксида азота и значение NO-синтаз в миокарде: молекулярные и цитофизиологические аспекты. В кн.: Сб. трудов I съезда физиологов СНГ (19-23 сентября 2005 г., Сочи, Дагомыс). М., Медицина, Здоровье, 2005, т. 2, с. 11.Arstall M.A., Sawyer D.B., Fukazawa R. and Kelly R.A. Cytokine-mediated apoptosis in cardiac myocytes: the role of inducible nitric oxide synthase induction and peroxynitrite generation. Circ. Res., 1999, v. 85, № 9, p. 829-840.Ashley E.A., Sears C.E., Bryant S.M. et al. Cardiac nitric oxide synthase 1 regulates basal and beta-adrenergic contractility in murine ventricular myocytes. Circulation, 2002, v. 105, № 25, p. 3011-3016.Balligand J.L., Kelly R.A., Marsden P.A. et al. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc. Natl Acad. Sci. USA, 1993, v. 90, № 1, p. 347-351.Balligand J.L., Kobzik L., Han X. et al. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J. Biol. Chem., 1995, v. 270, № 24, p. 14582-14586.Barouch L.A., Harrison R.W., Skaf M.W. et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature, 2002, v. 416, № 6878, p. 337-339.Bassani J.W., Bassani R.A. and Bers D.M. Relaxation in rabbit and rat cardiac cells: species dependent differences in cellular mechanisms. J. Physiol. 1994, v. 476, p. 279-293.Bates T.E., Loesch A., Burnstock G. and Clark J.B. Mitochondrial nitric oxide synthase: A ubiquitous regulator of oxidative phosphorylation? Biochem. Biophys. Res. Comm., 1996, v. 218, p. 40-44.Belevych A.E. and Harvey R.D. Muscarinic inhibitory and stimulatory regulation of the L-type Ca2+ current is not altered in cardiac ventricular myocytes from mice lacking endothelial nitric oxide synthase. J. Physiol., 2000, v. 528, p. 279-289.Bers D.M. Cardiac excitation-contraction coupling. Nature, 2002, v. 415, p. 198-205.Bloch W., Addicks K., Hescheler J. and Fleischmann B.K. Nitric oxide synthase expression and function in embryonic and adult cardiomyocytes. Microsc. Res. Tech., 2001, v. 55, № 4, p. 259-269.Bloch W., Fan Y., Han J. et al. Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to displacement of Gi proteins. J. Cell. Biol., 2001, v. 154, № 4, p. 753-761.Brini M. Ryanodine receptor defects in muscle genetic diseases. Biochem. Biophys. Res. Commun., 2004, v. 322, p. 1245-1255.Champion H.C., Georgakopoulos D., Takimoto E. et al. Modulation of in vivo cardiac function by myocyte-specific nitric oxide synthase-3. Circ. Res., 2004, v. 94, № 5, p. 657-663.Champion H.C., Skaf M.W. and Hare J.M. Role of nitric oxide in the pathophysiology of heart failure. Heart Fail Rev., 2003, v. 8, № 1, p. 35-46.Cohen R.A. The role of nitric oxide and other endothelium-derived vasoactive substances in vascular disease. Prog. Cardiovasc. Dis., 1995, v. 38, p. 105-128.Damy T., Ratajczak P., Shah A.M. et al. Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet, 2004, v. 363, № 9418, p. 1365-1367.Danson E.J., Zhang Y.H., Sears C.E. et al. Disruption of inhibitory G-proteins mediates a reduction in atrial beta-adrenergic signaling by enhancing eNOS expression DANSON: Augmented eNOS signaling in atrial myocytes. Cardiovasc. Res., 2005, v. 67, № 4, p. 613-23;.Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am. J. Physiol., 1983, v. 245, p. C1-C14.Ferdinandy P., Panas D. and Schulz R. Peroxynitrite contributes to spontaneous loss of cardiac efficiency in isolated working rat hearts. Am. J. Physiol., 1999, v. 276, p. H1861-H1867.Feron O., Belhassen L., Kobzik L. et al. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J. Biol. Chem., 1996, v. 271, № 37, p. 22810-22814.Feron O., Han X. and Kelly R.A. Muscarinic cholinergic signaling in cardiac myocytes: dynamic targeting of M2AChR to sarcolemmal caveolae and eNOS activation. Life Sci., 1999, v. 64, № 6-7, p. 471-477.Fill M., Zahradnikova A., Villalba-Galea C.A. et al. Ryanodine receptor adaptation. J. Gen. Physiol., 2000, v. 116, № 6, p. 873-882.Forstermann U., Boissel J.P. and Kleinert H. Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J., 1998, v. 12, № 10, p. 773-790.Fukuchi M., Hussain S.N.A. and Giaid A. Heterogeneous expression and activity of endothelial and inducible nitric oxide synthases in end-stage human heart failure. Their relation to lesion site and b-adrenergic receptor therapy. Circulation, 1998, v. 98, p. 132-139.Gallo M.P., Malan D., Bedendi I. et al. Regulation of cardiac calcium current by NO and cGMP-modulating agents. Pflugers Arch., 2001, v. 441, № 5, p. 621-628.Godecke A., Molojavyi A., Heger J. et al. Myoglobin protects the heart from inducible nitric-oxide synthase (iNOS)-mediated nitrosative stress. J. Biol. Chem., 2003, v. 278, p. 21761-21766.Godecke A. and Schrader J. The Janus faces of NO? Circ. Res., 2004, v. 94, № 6, p. e55.Gratton J.P., Bernatchez P. and Sessa W.C. Caveolae and caveolins in the cardiovascular system. Circ. Res., 2004, v. 94, p. 1408.Han X., Kobzik L., Severson D. and Shimoni Y. Characteristics of nitric oxide-mediated cholinergic modulation of calcium current in rabbit sino-atrial node. J. Physiol., 1998, v. 509, p. 741-754.Han X., Shimoni Y. and Giles W.R. An obligatory role for nitric oxide in autonomic control of mammalian heart rate. J. Physiol., 1994, v. 476, p. 309-314.Hare J.M. Oxidative stress and apoptosis in heart failure progression. Circ. Res., 2001, v. 89, № 3, p. 198-200.Hare J.M. Nitric oxide and excitation-contraction coupling. J. Mol. Cell. Cardiol., 2003, v. 35, № 7, p. 719-729.Hare J.M. Spatial confinement of isoforms of cardiac nitric-oxide synthase: unravelling the complexities of nitric oxide's cardiobiol- ogy. Lancet, 2004, v. 363, № 9418, p. 1338-1339.Hare J.M., Kim B., Flavahan N.A. et al. Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart. J. Clin. Invest., 1998, v. 101, № 6, p. 1424-1431.Hare J.M., Lofthouse R.A., Juang G.J. et al. Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure. Circ. Res., 2000, v. 86, № 10, p. 1085-1092.Hare J.M. and Stamler J.S. NOS: modulator, not mediator of cardiac performance. Nat. Med., 1999, v. 5, № 3, p. 273-274.Hassall C.J., Saffrey M.J., Belai A. et al. Nitric oxide synthase immunoreactivity and ADPH-diaphorase activity in a subpopulation of intrinsic neurones of the guinea-pig heart. Neurosci. Lett., 1992, v. 143, № 1-2, p. 65-68.Heger J., Godecke A., Flogel U. et al. Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction. Circ. Res., 2002, v. 90, p. 93-99.Herring N., Danson E.J. and Paterson D.J. Cholinergic control of heart rate by nitric oxide is site specific. News Physiol. Sci., 2002, v. 17, p. 202-206.Herring N., Rigg L., Terrar D.A. and Paterson D.J. NO-cGMP pathway increases the hyperpolarisation-activated current, I(f), and heart rate during adrenergic stimulation. Cardiovasc. Res., 2001, v. 52, p. 446-453.Ignarro L.J., Byrns R.E., Buga G.M. and Wood K.S. Endothelium-derived relaxing factor from pulmonary artery and vein posses pharmacological and chemical properties identical to those of nitric oxide radical. Circ. Res., 1987, v. 61, p. 866-879.Ji G.J., Fleischmann B.K., Bloch W. et al. Regulation of the L-type Ca2+ channel during cardiomyogenesis: switch from NO to adenylyl cyclase-mediated inhibition. FASEB J., 1999, v.13, № 2, p. 313-324.Kanai A. and Peterson J. Function and regulation of mitochondrially produced nitric oxide in cardiomyocytes. Am. J. Physiol. Heart. Circ. Physiol., 2004, v. 286, № 1, p. H11-H12.Kaye D.M., Wiviott S.D., Balligand J.L. et al. Frequency-dependent activation of a constitutive nitric oxide synthase and regulation of contractile function in adult rat ventricular myocytes. Circ. Res., 1996, v. 78, № 2, p. 217-224.Kelly R.A. and Smith T.W. Cytokines and cardiac contractile function. Circulation, 1997, v. 95, № 4, p. 778-781.Klimaschewski L., Kummer W., Mayer B. et al. Nitric oxide synthase in cardiac nerve fibers and neurons of rat and guinea pig heart. Circ. Res., 1992, v. 71, № 6, p. 1533-1537.Levin K.R. and Page E. Quantitative studies on plasmalemmal folds and caveolae of rabbit ventricular myocardial cells. Circ. Res., 1980, v. 46, p. 244-255.Litwin S.E., Zhang D. and Bridge J.H. Dyssynchronous Ca2+ sparks in myocytes from infarcted hearts. Circ. Res., 2000, v. 87, p. 1040-1047.Lokuta A.J., Maertz N.A., Meethal S.V. et al. Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure. Circulation, 2005, v. 111, № 8, p. 988-995.Marletta M.A. Nitric oxide: biosynthesis and biological significance. Trends Biochem. Sci., 1989, v.14, № 12, p. 488-492.Marletta M.A. Nitric oxide synthase structure and mechanism. J. Biol. Chem., 1993, v. 268, p. 12231-12234.Massion P.B. and Balligand J.L. Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice. J. Physiol., 2003, v. 546, p. 63-75.Massion P.B., Feron O., Dessy C. and Balligand J.L. Nitric oxide and cardiac function: ten years after, and continuing. Circ. Res., 2003, v. 93, p. 388-398.Michel J.B., Feron O., Sase K. et al. Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase. J. Biol. Chem., 1997, v. 272, № 41, p. 25907-25912.Mohan R.M., Choate J.K., Golding S. et al. Peripheral presynaptic pathway reduces the heart rate response to sympathetic activation following exercise training: role of NO. Cardiovasc. Res., 2000, v. 47, № 1, p. 90-98.Moncada S. and Erusalimsky J.D. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat. Rev. Mol. Cell. Biol., 2002, v. 3, p. 214-220.Mungrue I.N., Stewart D.J. and Husain M. The Janus faces of iNOS. Circ. Res., 2003, v. 93, № 7, p. e74.Musialek P., Lei M., Brown H.F. et al. Nitric oxide can increase heart rate by stimulating the hyperpolarization-activated inward current, I(f). Circ. Res., 1997, v. 81, p. 60-68.Okhotin V.E. and Goncharuk V.D. Nitric oxide containing and receptor terminals in the rabbit heart. Medicina, 1996, v. 4, № 32, p. 111-112.Okhotin V.E. and Kupriyanov V.V. Neurovascular relationships in the human neocortex. Neurosci. Behav. Physiol., 1997, v. 27, № 5, p. 482-488.Oyama J., Shimokawa H., Momii H. et al. Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo. J. Clin. Invest., 1998, v. 101, p. 2207-2214.Palmer R.M., Ferrige A.G. and Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 1987, v. 327, № 6122, p. 524-526.Paton J.F., Kasparov S. and Paterson D.J. Nitric oxide and autonomic control of heart rate: a question of specificity. Trends Neurosci., 2002, v. 25, № 12, p. 626-631.Petroff M.G., Kim S.H., Pepe S. et al. Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nat. Cell Biol., 2001, v. 3, № 10, p. 867-873.Piech A., Dessy C., Havaux X. et al. Differential regulation of nitric oxide synthase and their allosteric regulators in heart and vessels of hypertensive rats. Cardiovasc. Res., 2003, v. 57, № 2, p. 456-467.Piech A., Massart P.E., Dessy C. et al. Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy. Am. J. Physiol., 2002, v. 282, p. H219-231.Richardson R.J., Grkovic I. and Anderson C.R. Immunohistochemical analysis of intracardiac ganglia of the rat heart. Cell Tissue Res., 2003, v. 314, p. 337-350.Sah R., Ramirez R.J. and Backx P.H. Modulation of Ca2+ release in cardiac myocytes by changes in repolarization rate: role of phase-1 action potential repolarization in excitation-contraction coupling. Circ. Res., 2002, v. 90, p. 165-173.Saito T., Hu F., Tayara L. et al. Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure. Am. J. Physiol. Heart. Circ. Physiol., 2002, v. 283, № 1, p. H339-H345.Schroder F., Klein G., Fiedler B. et al. Single L-type Ca(2+) channel regulation by cGMP-dependent protein kinase type I in adult cardiomyocytes from PKC I transgenic mice. Cardiovasc. Res., 2003, v. 60, № 2, p. 268-277.Schulz R., Nava E. and Moncada S. Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium. Br. J. Pharmacol., 1992, v. 105, p. 575-580.Sears C.E., Bryant S.M., Ashley E.A. et al. Cardiac neuronal nitric oxide synthase isoform regulates myocardial contraction and calcium handling. Circ. Res., 2003, v. 92, № 5, p. e52-e59.Sears C.E., Choate J.K. and Paterson D.J. Inhibition of nitric oxide synthase slows heart rate recovery from cholinergic activation. J. Appl. Physiol., 1998, v. 84, № 5, p. 1596-1603.Simons K.and Toomre D. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol., 2000, № 1, p. 31-39.Sitsapesan R. and Williams A.J. Do inactivation mechanisms rather than adaptation hold the key to understanding ryanodine receptor channel gating? J. Gen. Physiol., 2000, v. 116, № 6, p. 867-872.Sjaastad I., Wasserstrom J.A. and Sejersted O.M. Heart failure - a challenge to our current concepts of excitation-contraction coupling. J. Physiol., 2003, v. 546, p. 33-47.Snyder S.H. and Bredt D.S. Nitric oxide as a neuronal messenger. Trends Pharmacol. Sci., 1991, v. 12, № 4, p. 125-128.Snyder S.H. Janus faces of nitric oxide. Nature, 1993, v. 364, № 6438, p. 577.Sosunov A.A., Hassall C.J., Loesch A. et al. Nitric oxide synthase-containing neurones and nerve fibres within cardiac ganglia of rat and guinea-pig: an electron-microscopic immunocytochemical study. Cell Tissue Res., 1996, v. 284, № 1, p. 19-28.Tanaka K., Hassall C.J. and Burnstock G. Distribution of intracardiac neurones and nerve terminals that contain a marker for nitric oxide, NADPH-diaphorase, in the guinea-pig heart. Cell Tissue Res., 1993, v. 273, № 2, p. 293-300.Torre-Amione G., Kapadia S., Benedict C. et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: A report from the studies of left ventricular dysfunction (SOLVD). J. Am. Coll. Cardiol., 1996, v. 27, № 5, p. 1201-1206.Ungureanu-Longrois D., Balligand J.L., Kelly R.A. and Smith T.W. Myocardial contractile dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes. J. Mol. Cell Cardiol., 1995, v. 27, № 1, p. 155-167.Vandecasteele G., Verde I., Rucker-Martin C. et al. Cyclic GMP regulation of the L-type Ca(2+) channel current in human atrial myocytes. J. Physiol., 2001, v. 533, p. 329-340.Vanin A.F., Malenkova I.V. and Serezhenkov V.A. Iron catalyzes both decomposition and synthesis of S-nitrosothiols: optical and electron paramagnetic resonance studies. Nitric Oxide, 1997, v. 1, № 3, p. 191-203.Willmott N., Sethi J.K., Walseth T.F. et al. Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway. J. Biol. Chem., 1996, v. 271, p. 3699-3705.Xu K.Y., Huso D.L., Dawson T.M. et al. Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc. Natl. Acad. Sci. USA, 1999, v. 96, № 2, p. 657-662.Xu L., Eu J.P., Meissner G. and Stamler J.S. Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science, 1998, v. 279, № 5348, p. 234-237.Yano M., Ikeda Y. and Matsuzaki M. Altered intracellular Ca2+ handling in heart failure. J. Clin. Invest., 2005, v. 115, № 3, p. 556-564.