МОДУЛЯЦИЯ АКТИВНОСТИ РАЗЛИЧНЫХ СИНТАЗ ОКСИДА АЗОТА В КАЧЕСТВЕ ПОДХОДА К ТЕРАПИИ ЭНДОТЕЛИАЛЬНОЙ ДИСФУНКЦИИ

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

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. 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. 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.

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