Статья
Эндогенные кардиотонические стероиды: клинические перспективы
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.
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