arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2008-14-3-220-232arthyper-1232Research ArticleОБЗОРREVIEWЭндогенные кардиотонические стероиды: клинические перспективыEndogenous cardiotonic steroids: clinical perspectivesФедороваО.FedorovaO. V.noemail@neicon.ruКоростовцеваЛ.KorostovtsevaL.noemail@neicon.ruШапироД.ShapiroJ.noemail@neicon.ruБагровА.BagrovA.noemail@neicon.ruНациональный институт старения, Национальные институты здоровьяРоссияNational Institute of Aging, National Institutes of HealthRussian FederationФедеральный центр сердца, крови и эндокринологии им. В.А. АлмазоваРоссияV.A. Almazov Heart, Blood and Endocrinology CenterRussian FederationМедицинский колледж Университета ТоледоРоссияCollege of Medicine, University of ToledoRussian Federation200828062008143220232Copyright © Федорова О.V., Коростовцева Л., Шапиро Д., Багров А., 20082008Федорова О., Коростовцева Л., Шапиро Д., Багров А.Fedorova O.V., Korostovtseva L., Shapiro J., Bagrov A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/1232

В настоящее время выявлено несколько эндогенных кардиотонических стероидов, или дигиталис-подобных факторов, у человека; среди них уабаин, относящийся к классу карденолидов, и маринобуфагенин, из класса буфадиенолидов, изучены наиболее подробно. Физиологической функцией кардиотонических стероидов является поддержание гомеостаза натрия и регуляция натрийуреза на уровне почек. Эндогенные кардиотонические стероиды, связываясь с Na/K-АТФ-азой, не только ингибируют трансмембранный транспорт моновалентных катионов, а также активируют Src-EGF-опосредованный путь клеточной сигнализации. У крыс линии Dahl с соль-индуцированной артериальной гипертензией эндогенный уабаин действует как нейрогормон, стимулируя высвобождение маринобуфагенина, обладающего натриуретическим и сосудосуживающим свойствами. У ряда больных полиморфизм гена альфа-аддуцина на фоне повышения уровня эндогенного уабаина приводит к активации Na/K-АТФ-азы в почечных канальцах и ретенции натрия, что является триггером развития гипертензии. Эндогенные кардиотонические стероиды также вносят вклад в патогенез хронической сердечной недостаточности, преэклампсии и сахарного диабета. Иммунонейтрализация, антагонизм рецепторов кардиотонических стероидов, ингибирование протеин-киназы С и активация протеин-киназы G являются потенциальными подходами к фармакологическому антагонизму нежелательных эффектов кардиотонических стероидов.

Several endogenous digitalis-like cardiotonic steroids (CTS) have been identified in humans, including endogenous ouabain, a cardenolide, and marinobufagenin which belongs to a class of bufadienolides. The main function of CTS is maintenance of sodium homeostasis and regulation of natriuretic function. Endogenous cardiotonic steroids bind to the Na/K-ATPase and exhibit two kinds of effects, inhibition of transmembrane transport of monovalent cations, and induction of a complex cascade of cell signaling. In Dahl salt-sensitive rats with NaCl-induced hypertension, endogenous ouabain, acting as a neurohormone stimulates adrenocortical marinobufagenin, which raises blood pressure via inhibition of vascular Na/K-ATPase. In a subgroup of hypertensive subjects, which possess a polymorphism of alpha-adducin gene, elevated levels of endogenous ouabain activate renotubular Na/K-ATPase and induce renal sodium retention. Elevated levels of CTS also contribute to pathogenesis of congestive heart failure, preeclampsia, and diabetes mellitus. The approaches to pharmacological antagonism of the effects of CTS include blockade of CTS receptor site on the Na/K-ATPase, immunoneutralization, and interactions at the levels of Na/K-ATPase phosphorylation/dephosphorylation by protein kinases С and G.

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