bmjourБайкальский медицинский журналBaikal Medical Journal2949-0715Irkutsk State Medical University10.57256/2949-0715-2024-2-71-81bmjour-224Research ArticleЛекции для студентов, ординаторов и аспирантовLectures for students, residents and postgraduatesВЛИЯНИЕ ТКАНЕВЫХ АНГИОТЕНЗИНОВ НА ЭЛЕМЕНТЫ КАРДИОВАСКУЛЯРНОЙ СИСТЕМЫ (ЛЕКЦИЯ)THE INFLUENCE OF TISSUE ANGIOTENSINS ON ELEMENTS OF THE CARDIOVASCULAR SYSTEM (LECTURE)https://orcid.org/0000-0003-4217-0617ГуцолЛюдмила ОлеговнаGutsolLiudmila O

к.б.н., доцент, доцент кафедры патологической физиологии и клинической лабораторной диагностики ФГБОУ ВО ИГМУ Минздрава России, Россия, 664003, г. Иркутск, ул. Красного Восстания, 1. 

Cand. Sci. (Вiol.), associate professor, associate professor of Department of Pathological Physiology and Clinical Laboratory Diagnostics, Irkutsk State Medical University, Russia, 664003, Irkutsk, st. Krasnogo Vosstaniya, 1

gutzol@list.ruhttps://orcid.org/0000-0001-7504-4938ЕгороваИрина ЭдуардовнаEgorovaIrina E

к.м.н., доцент, доцент кафедры химии и биохимии ФГБОУ ВО ИГМУ Минздрава России, Россия, 664003, г. Иркутск, ул. Красного Восстания, 1

Cand. Sci. (Med.), associate professor, associate professor of the Department of Chemistry and Biochemistry, Irkutsk State Medical University, Russia, 664003, Irkutsk, st. Krasnogo Vosstaniya, 1

ФГБОУ ВО «Иркутский государственный медицинский университет» Минздрава РоссииРоссияIrkutsk State Medical University, Russia, 664003, Irkutsk, st. Krasnogo Vosstaniya, 1Russian Federation202410062024327181Copyright © Гуцол Л.О., Егорова И.Э., 20242024Гуцол Л.О., Егорова И.Э.Gutsol L.O., Egorova I.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.bmjour.ru/jour/article/view/224Актуальность

Актуальность. Ренин-ангиотензиновая система является на сегодняшний день одним из старейших и наиболее изученных пептидных каскадов. Понимание работы этой системы является актуальной задачей для изучения в медицинских высших учебных заведениях. Ренин-ангиотензиновая система является важной регуляторной системой, поддерживающей метаболизм и функционирование многих органов, в том числе сосудов и миокарда. Поскольку сердечно-сосудистые заболевания являются основной причиной смертности, то изучение позитивных и негативных механизмов регуляции сердечно-сосудистой системы является актуальной задачей на современном этапе.

Цель

Цель. Рассмотреть современные представления о ренин-ангиотензиновой системе и ее роли в регуляции гомеостаза.

Результаты

Результаты. В лекции рассмотрены классическая и тканевая ренин-ангиотензиновая система, основные метаболиты-ангиотензины, пути их образования и ферменты, катализирующие эти превращения. Показаны эффекты, реализуемые ангиотензинами через различные рецепторы. Рассмотрена современная точка зрения на уровни организации ренин-ангиотензиновой системы в организме и взаимосвязь различных ангиотензинов-антагонистов друг с другом.

Заключение

Заключение. Ренин-ангиотензиновая система – одна из наиболее сложных систем гормональной регуляции, включающая несколько органов, которые взаимодействуют, регулируя множество функций организма. Эффекты ангиотензинов сложны и часто противоположны. Дисбаланс в регуляции гомеостаза ангиотензинов приводит к нарушениям метаболизма органов и тканей и проявляется при патологиях, при которых распространены воспалительные, гипертрофические и фиброзные явления, а также связаны с развитием хронических заболеваний, поражающих различные органы и ткани организма.

Relevance

Relevance. The renin-angiotensin system is today one of the oldest and most studied peptide cascades. Understanding the operation of this system is an urgent task for study in medical higher education institutions. The renin-angiotensin system is an important regulatory system that supports the metabolism and functioning of many organs, including blood vessels and the myocardium. Since cardiovascular diseases are the main cause of mortality, the study of positive and negative mechanisms of regulation of the cardiovascular system is an urgent task at the present stage.

Aim

Aim. Consider modern ideas about the renin-angiotensin system and its role in the regulation of homeostasis.

Results

Results. The lecture discusses the classical and tissue renin-angiotensin system, the main angiotensin metabolites, the pathways of their formation and the enzymes that catalyze these transformations. The effects realized by angiotensins through various receptors are shown. The modern point of view on the levels of organization of the renin-angiotensin system in the body and the relationship of various angiotensin antagonists with each other is considered.

Conclusion

Conclusion. The renin-angiotensin system is one of the most complex systems of hormonal regulation, including several organs that interact to regulate many body functions. The effects of angiotensins are complex and often opposite. An imbalance in the regulation of angiotensin homeostasis leads to metabolic disorders of organs and tissues and manifests itself in pathologies in which inflammatory, hypertrophic and fibrotic phenomena are common, and are also associated with the development of chronic diseases affecting various organs and tissues of the body.

ангиотензинренинангиотензинпревращающий ферментангиотензинпревращающий фермент 2тканевая ренин-ангиотензиновая система.angiotensinreninangiotensin-converting enzymeangiotensin converting enzyme 2tissue renin-angiotensin systemReferencesFyhrquist F., Saijonmaa O. Renin-angiotensin system revisited. J. Intern. Med. 2008; 264(3): 224–236. DOI: 10.1111/j.1365-2796.2008.01981.xFyhrquist F., Saijonmaa O. Renin-angiotensin system revisited. J. Intern. Med. 2008; 264(3): 224–236. DOI: 10.1111/j.1365-2796.2008.01981.xFountain J.H., Kaur J., Lappin S.L. Physiology, Renin Angiotensin System. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.Fountain J.H., Kaur J., Lappin S.L. Physiology, Renin Angiotensin System. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.Максимов М.Л., Дралова О.В., Стародубцев А.К. Антагонисты АТ1-рецепторов ангиотензина II, ингибиторы ангиотензинпревращающего фермента в регуляции гемодинамики и активности ангиотензин-альдостероновой системы. Фокус на органопротективные эффекты. Кардиоваскулярная терапия и профилактика. 2010;9(2):115-124 [Maksimov M.L., Dralova O.V., Starodubtsev A.K. Antagonists of AT1 receptors of angiotensin II, inhibitors of angiotensin-converting enzyme in the regulation of hemodynamics and the activity of the angiotensin-aldosterone system. Focus on organoprotective effects. Cardiovascular therapy and prevention. 2010 9(2):115-124 (In Russian)]. https://cardiovascular.elpub.ru/jour/article/view/2055/1710?locale=ru_RU [дата доступа: 21.05.2024].Максимов М.Л., Дралова О.В., Стародубцев А.К. Антагонисты АТ1-рецепторов ангиотензина II, ингибиторы ангиотензинпревращающего фермента в регуляции гемодинамики и активности ангиотензин-альдостероновой системы. Фокус на органопротективные эффекты. Кардиоваскулярная терапия и профилактика. 2010;9(2):115-124 [Maksimov M.L., Dralova O.V., Starodubtsev A.K. Antagonists of AT1 receptors of angiotensin II, inhibitors of angiotensin-converting enzyme in the regulation of hemodynamics and the activity of the angiotensin-aldosterone system. Focus on organoprotective effects. Cardiovascular therapy and prevention. 2010 9(2):115-124 (In Russian)]. https://cardiovascular.elpub.ru/jour/article/view/2055/1710?locale=ru_RU [дата доступа: 21.05.2024].Vargas Vargas R.A., Varela Millán J.M., Fajardo Bonilla E. Renin-angiotensin system: Basic and clinical aspects-A general perspective. Endocrinol Diabetes Nutr (Engl Ed). 2022;(1):52-62. DOI: 10.1016/j.endien.2022.01.005Vargas Vargas R.A., Varela Millán J.M., Fajardo Bonilla E. Renin-angiotensin system: Basic and clinical aspects-A general perspective. Endocrinol Diabetes Nutr (Engl Ed). 2022;(1):52-62. DOI: 10.1016/j.endien.2022.01.005van Kats J.P., de Lannoy L.M., Jan Danser A.H. et al. Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo. Hypertension. 1997;30(1 Pt 1):42-49. DOI: 10.1161/01.hyp.30.1.42van Kats J.P., de Lannoy L.M., Jan Danser A.H. et al. Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo. Hypertension. 1997;30(1 Pt 1):42-49. DOI: 10.1161/01.hyp.30.1.42Carey R.M., Wang Z.Q., Siragy H.M. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension. 2000;35(1 Pt 2): 155-163. DOI: 10.1161/01.hyp.35.1.155Carey R.M., Wang Z.Q., Siragy H.M. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension. 2000;35(1 Pt 2): 155-163. DOI: 10.1161/01.hyp.35.1.155Kaschina E., Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12(2):70-88. DOI: 10.1080/08037050310001057Kaschina E., Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12(2):70-88. DOI: 10.1080/08037050310001057Eguchi S., Kawai T., Scalia R., Rizzo V. Understanding Angiotensin II Type 1 Receptor Signaling in Vascular Pathophysiology. Hypertension. 2018;71(5):804-810. DOI: 10.1161/HYPERTENSIONAHA.118.10266Eguchi S., Kawai T., Scalia R., Rizzo V. Understanding Angiotensin II Type 1 Receptor Signaling in Vascular Pathophysiology. Hypertension. 2018;71(5):804-810. DOI: 10.1161/HYPERTENSIONAHA.118.10266Capric V., Chandrakumar H.P., Celenza-Salvatore J.N., Makaryus A. The Role of the Renin-Angiotensin-Aldosterone System in Cardiovascular Disease: Pathogenetic Insights and Clinical Implications. Renin-Angiotensin Aldosterone System. IntechOpen; 2021. Available from: doi.org/10.5772/intechopen.Capric V., Chandrakumar H.P., Celenza-Salvatore J.N., Makaryus A. The Role of the Renin-Angiotensin-Aldosterone System in Cardiovascular Disease: Pathogenetic Insights and Clinical Implications. Renin-Angiotensin Aldosterone System. IntechOpen; 2021. Available from: doi.org/10.5772/intechopen.Holst J.P., Soldin O.P., Guo T., Soldin S.J. Steroid hormones: relevance and measurement in the clinical laboratory. Clin Lab Med. 2004;24(1):105-118. DOI: 10.1016/j.cll.2004.01.004Holst J.P., Soldin O.P., Guo T., Soldin S.J. Steroid hormones: relevance and measurement in the clinical laboratory. Clin Lab Med. 2004;24(1):105-118. DOI: 10.1016/j.cll.2004.01.004Paul M., Poyan Mehr A., Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86(3):747-803. DOI: 10.1152/physrev.00036.2005Paul M., Poyan Mehr A., Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86(3):747-803. DOI: 10.1152/physrev.00036.2005Pacurari M., Kafoury R., Tchounwou P.B., Ndebele K. The Renin-Angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam. 2014;2014: 689360. DOI: 10.1155/2014/689360Pacurari M., Kafoury R., Tchounwou P.B., Ndebele K. The Renin-Angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam. 2014;2014: 689360. DOI: 10.1155/2014/689360Ahmad S., Varagic J., Groban L. et al. Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate. Curr Hypertens Rep. 2014;16(5):429. DOI: 10.1007/s11906-014-0429-9Ahmad S., Varagic J., Groban L. et al. Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate. Curr Hypertens Rep. 2014;16(5):429. DOI: 10.1007/s11906-014-0429-9Esser N., Zraika S. Neprilysin Inhibitors and Angiotensin (1-7) in COVID-19. Br J Cardiol. 2020;27(4):109-111. DOI: 10.5837/bjc.2020.031Esser N., Zraika S. Neprilysin Inhibitors and Angiotensin (1-7) in COVID-19. Br J Cardiol. 2020;27(4):109-111. DOI: 10.5837/bjc.2020.031Yu L., Yuan K., Phuong H.T. et al. Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor. Peptides. 2016;86:33-41. DOI: 10.1016/j.peptides.2016.09.009Yu L., Yuan K., Phuong H.T. et al. Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor. Peptides. 2016;86:33-41. DOI: 10.1016/j.peptides.2016.09.009Varagic J., Ahmad S., Nagata S., Ferrario C.M. ACE2: angiotensin II/angiotensin-(1-7) balance in cardiac and renal injury. Curr Hypertens Rep. 2014;16(3):420. DOI: 10.1007/s11906-014-0420-5Varagic J., Ahmad S., Nagata S., Ferrario C.M. ACE2: angiotensin II/angiotensin-(1-7) balance in cardiac and renal injury. Curr Hypertens Rep. 2014;16(3):420. DOI: 10.1007/s11906-014-0420-5Martyniak A., Tomasik P.J. A New Perspective on the Renin-Angiotensin System. Diagnostics (Basel). 2022;13(1):16. DOI: 10.3390/diagnostics13010016Martyniak A., Tomasik P.J. A New Perspective on the Renin-Angiotensin System. Diagnostics (Basel). 2022;13(1):16. DOI: 10.3390/diagnostics13010016Januzzi J.L. Jr, Ibrahim N.E. Renin-Angiotensin System Blockade in Heart Failure: More to the Picture Than Meets the Eye. J Am Coll Cardiol. 2017;69(7):820-822. DOI: 10.1016/j.jacc.2016.10.083Januzzi J.L. Jr, Ibrahim N.E. Renin-Angiotensin System Blockade in Heart Failure: More to the Picture Than Meets the Eye. J Am Coll Cardiol. 2017;69(7):820-822. DOI: 10.1016/j.jacc.2016.10.083Paz Ocaranza M., Riquelme J.A., García L. et al. Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol. 2020;17(2):116-129. DOI: 10.1038/s41569-019-0244-8Paz Ocaranza M., Riquelme J.A., García L. et al. Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol. 2020;17(2):116-129. DOI: 10.1038/s41569-019-0244-8Kaschina E., Unger T. Angiotensin AT1/AT2 Receptors: Regulation, Signalling and Function. Blood Pressure. 2009;12:2:70-88. DOI: 10.1080/08037050310001057Kaschina E., Unger T. Angiotensin AT1/AT2 Receptors: Regulation, Signalling and Function. Blood Pressure. 2009;12:2:70-88. DOI: 10.1080/08037050310001057van Thiel B.S., van der Pluijm I., te Riet L. et al. The renin-angiotensin system and its involvement in vascular disease. Eur J Pharmacol. 2015;763(Pt A):3-14. DOI: 10.1016/j.ejphar.2015.03.090van Thiel B.S., van der Pluijm I., te Riet L. et al. The renin-angiotensin system and its involvement in vascular disease. Eur J Pharmacol. 2015;763(Pt A):3-14. DOI: 10.1016/j.ejphar.2015.03.090Verma K., Pant M., Paliwal S. et al. An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update. Front Pharmacol. 2021;12:734917. DOI: 10.3389/fphar.2021.734917Verma K., Pant M., Paliwal S. et al. An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update. Front Pharmacol. 2021;12:734917. DOI: 10.3389/fphar.2021.734917Beyazit Y., Purnak T., Guven G.S., Haznedaroglu I.C. Local bone marrow Renin-Angiotensin system and atherosclerosis. Cardiol Res Pract. 2010;2011:714515. DOI: 10.4061/2011/714515Beyazit Y., Purnak T., Guven G.S., Haznedaroglu I.C. Local bone marrow Renin-Angiotensin system and atherosclerosis. Cardiol Res Pract. 2010;2011:714515. DOI: 10.4061/2011/714515Flores-Monroy J., Lezama-Martínez D., Martínez-Aguilar L. Function of renin angiotensin system on heart failure. Journal of Integrative Cardiology. 2016;2(5): 380386. DOI: 10.15761/JIC.1000180Flores-Monroy J., Lezama-Martínez D., Martínez-Aguilar L. Function of renin angiotensin system on heart failure. Journal of Integrative Cardiology. 2016;2(5): 380386. DOI: 10.15761/JIC.1000180Padia S.H., Carey R.M. AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch. 2013;465(1):99-110. DOI: 10.1007/s00424-012-1146-3Padia S.H., Carey R.M. AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch. 2013;465(1):99-110. DOI: 10.1007/s00424-012-1146-3Patel V.B., Zhong J.C., Grant M.B., Oudit G.Y. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure. Circ Res. 2016;118(8):1313-1326. DOI: 10.1161/CIRCRESAHA.116.307708Patel V.B., Zhong J.C., Grant M.B., Oudit G.Y. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure. Circ Res. 2016;118(8):1313-1326. DOI: 10.1161/CIRCRESAHA.116.307708Suzuki S., Iida M., Hiroaki Y. et al. Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM. Commun Biol. 2022;5:707. DOI: 10.1038/s42003-022-03668-3Suzuki S., Iida M., Hiroaki Y. et al. Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM. Commun Biol. 2022;5:707. DOI: 10.1038/s42003-022-03668-3Poznyak A.V., Bharadwaj D., Prasad G. et al. Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD. Int J Mol Sci. 2021;22(13):6702. DOI: 10.3390/ijms22136702Poznyak A.V., Bharadwaj D., Prasad G. et al. Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD. Int J Mol Sci. 2021;22(13):6702. DOI: 10.3390/ijms22136702Mehta J.K., Kaur G., Buttar H.S. et al. Role of the renin–angiotensin system in the pathophysiology of coronary heart disease and heart failure: Diagnostic biomarkers and therapy with drugs and natural products. Front. Physiol. Sec. Vascular Physiology. 2023;14. DOI:10.3389/fphys.2023.1034170Mehta J.K., Kaur G., Buttar H.S. et al. Role of the renin–angiotensin system in the pathophysiology of coronary heart disease and heart failure: Diagnostic biomarkers and therapy with drugs and natural products. Front. Physiol. Sec. Vascular Physiology. 2023;14. DOI:10.3389/fphys.2023.1034170Turner A.J. ACE2 Cell Biology, Regulation, and Physiological Functions. The Protective Arm of the Renin Angiotensin System (RAS). 2015;185-189. DOI:10.1016/B978-0-12-801364-9.00025-0Turner A.J. ACE2 Cell Biology, Regulation, and Physiological Functions. The Protective Arm of the Renin Angiotensin System (RAS). 2015;185-189. DOI:10.1016/B978-0-12-801364-9.00025-0Doggrell S.A., Wanstall J.C. Vascular chymase: pathophysiological role and therapeutic potential of inhibition, Cardiovascular Research. 2004;61(4):653-662. DOI:10.1016/j.cardiores.2003.11.029Doggrell S.A., Wanstall J.C. Vascular chymase: pathophysiological role and therapeutic potential of inhibition, Cardiovascular Research. 2004;61(4):653-662. DOI:10.1016/j.cardiores.2003.11.029Tchougounova E., Lundequist A., Fajardo I. et al. A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2. J. Biol. Chem. 2005;280:9291–9296. DOI: 10.1074/jbc.M410396200Tchougounova E., Lundequist A., Fajardo I. et al. A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2. J. Biol. Chem. 2005;280:9291–9296. DOI: 10.1074/jbc.M410396200

The authors declare that there are no conflicts of interest present.