pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2022-10-2-130-153pmedpharm-1068Research ArticleОБЗОРЫ, ЛЕКЦИИREVIEWS, LECTURESМОДУЛЯЦИЯ АКТИВНОСТИ РАЗЛИЧНЫХ СИНТАЗ ОКСИДА АЗОТА В КАЧЕСТВЕ ПОДХОДА К ТЕРАПИИ ЭНДОТЕЛИАЛЬНОЙ ДИСФУНКЦИИACTIVITY MODULATION OF VARIOUS NITRIC OXIDE SYNTASES AS AN APPROACH TO ENDOTHELIAL DYSFUNCTION THERAPYhttps://orcid.org/0000-0002-1116-3425КуркинД. В.KurkinD. V.

доктор фармацевтических наук, доцент, профессор кафедры клинической фармакологии и интенсивной терапии; первый заместитель директора НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Doctor of Sciences (Pharmacy), Associate Professor, Professor of the Department of Clinical Pharmacology and Intensive Care; First Deputy Director of the Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

strannik986@mail.ruhttps://orcid.org/0000-0002-6472-6906АбросимоваЕ. Е.AbrosimovaE. E.

аспирант кафедры фармакологии и фармации ИНМФО ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

post-graduate student of the Department of Pharmacology and Pharmacy, Institute of Continuing Medical and Pharmaceutical Education, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

abrosimova.volgmed@gmail.comhttps://orcid.org/0000-0003-4694-3066БакулинД. А.BakulinD. A.

кандидат медицинских наук, старший научный сотрудник лаборатории фармакологии сердечно-сосудистых средств НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Senior Researcher, Laboratory of Pharmacology of Cardiovascular Drugs, Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

mbfdoc@gmail.comhttps://orcid.org/0000-0002-1116-3425КовалевН. С.KovalevN. S.

аспирант кафедры фармакологии и фармации ИНМФО ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

post-graduate student of the Department of Pharmacology and Pharmacy, Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

kovalev.volgmed@gmail.comhttps://orcid.org/0000-0003-1903-8589ДубровинаМ. А.DubrovinaM. A.

аспирант кафедры фармакологии и фармации ИНМФО ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

post-graduate student of the Department of Pharmacology and Pharmacy, Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

dubrovina.volgmed@gmail.comhttps://orcid.org/0000-0003-0202-0008БорисовА. В.BorisovA. V.

научный сотрудник лаборатории фармакологии сердечно-сосудистых средств НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Researcher, Laboratory of Pharmacology of Cardiovascular Drugs, Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

 

borissow1978@rambler.ruhttps://orcid.org/0000-0002-6997-1601СтрыгинА. В.StryginA. V.

кандидат медицинских наук, доцент, заместитель директора НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Associate Professor, Deputy Director of the Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

 

drumsav@mail.ruhttps://orcid.org/0000-0002-7119-3546МорковинЕ. И.MorkovinE. I.

кандидат медицинских наук, доцент, заведующий лабораторией нейропсихофармакологии НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Associate Professor, Head of the Laboratory of Neuropsychopharmacology, Research Center of Innovative Pharma Products, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

 

e.i.morkovin@gmail.comhttps://orcid.org/0000-0001-7574-3923ТюренковИ. Н.TyurenkovI. N.

доктор медицинских наук, профессор, член-корреспондент РАН, заведующий лабораторией фармакологии сердечно-сосудистых средств НЦИЛС; заведующий кафедрой фармакологии и фармации Института НМФО ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Doctor of Sciences (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Pharmacology of Cardiovascular Drugs, Research Center of Innovative Pharma Products; Head of the Department of Pharmacology and Pharmacy, Institute of Continuing Medical and Pharmaceutical Education, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

fibfuv@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian Federation202202052022102130153Copyright © Куркин Д.В., Абросимова Е.Е., Бакулин Д.А., Ковалев Н.С., Дубровина М.А., Борисов А.В., Стрыгин А.В., Морковин Е.И., Тюренков И.Н., 20222022Куркин Д.В., Абросимова Е.Е., Бакулин Д.А., Ковалев Н.С., Дубровина М.А., Борисов А.В., Стрыгин А.В., Морковин Е.И., Тюренков И.Н.Kurkin D.V., Abrosimova E.E., Bakulin D.A., Kovalev N.S., Dubrovina M.A., Borisov A.V., Strygin A.V., Morkovin E.I., Tyurenkov I.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1068

Оксид азота как терапевтический подход к лечению сердечно-сосудистых заболеваний привлек внимание исследователей еще в конце XIX века. Являясь вазодилататором, оксид азота может быть уникальным терапевтическим средством для лечения гипертензии и, как следствие, почечной недостаточности и гипертрофии левого желудочка.

Цель

Цель. Проанализировать данные литературы о возможных путях модуляции активности различных синтаз оксида азота в качестве подхода к терапии эндотелиальной дисфункции.

Материалы и методы

Материалы и методы. При поиске материала для написания обзорной статьи использовали такие реферативные базы данных, как PubMed, Google Scholar, e-Library, и др. Поиск осуществлялся по публикациям за период с 1990 по 2021 гг. Параметрами для отбора литературы были выбраны следующие слова и словосочетания: оксид азота; NO-синтаза; эндотелиальная дисфункция; активатор NO-синтазы; ингибитор NO-синтазы.

Результаты

Результаты. В статье представлена история открытия оксида азота и его биологическая роль, процесс его биосинтеза, а также изоформ ферментов его синтезирующих (NOS): нейрональной – nNOS, эндотелиальной – eNOS и индуцибельной iNOS и их роль в нормальной и патологической физиологии. Рассмотрен процесс разобщения NOS (его молекулярных механизмов) в качестве основы эндотелиальной дисфункции. Представлены примеры фармакологической коррекции (BH4, ингибиторы аргиназы, статины, ресвератрол). Кроме того, описаны активаторы синтаз NO (кальция добезилат, cavNOxin, и некоторые активаторы транскрипции NOS), а также неселективные (L-NMMA, 1-NNA, L-NAME, ADMA, 546C88, VAS203) и селективные (L-NIO, 7-нитроиндазол, аминогуанидин, L-NIL, GW273629, GW274150, кавтратин) ингибиторы синтаз оксида азота.

Заключение

Заключение. Синтазы оксида азота продолжают оставаться перспективными мишенями для разработки средств, модулирующих их активность для коррекции различных патологий. В качестве терапевтического подхода модуляция активности синтазы оксида азота может быть реализована для лечения эндотелиальной дисфункции, являющейся причиной осложнений многих заболеваний.

Nitric oxide as a therapeutic approach to the treatment of cardiovascular diseases attracted the attention of researchers at the end of the 19th century. As a vasodilator, nitric oxide may be a unique therapeutic agent for the treatment of hypertension and, as a result, renal failure and left ventricular hypertrophy.

The aim of the article is to analyze the literature data on possible ways of modulating the activity of various nitric oxide synthases as an approach to the treatment of endothelial dysfunction.

Materials and methods

Materials and methods. When searching for materials for writing a review article, such abstract databases as PubMed, Google Scholar, e-Library, etc., were used. The search was carried out on the publications for the period from 1990 to 2021. The following words and phrases were chosen as parameters for the literature selection: nitric oxide; NO synthase; endothelial dysfunction; NO synthase activator; NO synthase inhibitor.

The following words and phrases were chosen as parameters for the literature selection:

Results

Results. The article presents the history of the nitric oxide discovery and its biological role, the process of its biosynthesis, as well as the isoforms of its synthesizing enzymes (NOS): neuronal – nNOS, endothelial – eNOS and inducible iNOS, and their role in normal and pathological physiology. The process of NOS uncoupling (its molecular mechanisms) has been considered as the basis of endothelial dysfunction.

The examples of the pharmacological correction (BH4, arginase inhibitors, statins, resveratrol) are presented. In addition, NO synthase activators (calcium dobesilate, cavNOxin, and some NOS transcription activators), as well as non-selective (L-NMMA, 1-NNA, L-NAME, ADMA, 546C88, VAS203) and selective (L-NIO, 7-nitroindazole, aminoguanidine, L-NIL, GW273629, GW274150, cavtratin) inhibitors of nitric oxide synthasehave been described.

Conclusion

Conclusion. Nitric oxide synthases continue to be promising targets for the development of agents that modulate their activity to correct various pathologies. As a therapeutic approach, modulation of the nitric oxide synthase activity can be implemented to treat endothelial dysfunction, which is the cause for complications of many diseases.

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