Антигипертензивная эффективность и влияние на маркеры эндотелиальной функции селективного бета-адреноблокатора небиволола у больных мягкой и умеренной артериальной гипертонией тема диссертации и автореферата по ВАК РФ 14.00.06, кандидат медицинских наук Спасская, Марианна Борисовна

• Спасская, Марианна Борисовна
• кандидат медицинских наук
• 2004

Оглавление диссертации кандидат медицинских наук Спасская, Марианна Борисовна

Список условных обозначений.

ВВЕДЕНИЕ.

ГЛАВА 1. ОБЗОР ЛИТЕРАТУРЫ.

1.1. Дисфункция эндотелия.

1.1.1. Функции эндотелия.

111.2. Роль оксида азота в модуляции физиологической функции эндотели.

1.1.3. Эндотелиальные факторы.

1.2. NO и ДЭ в патогенезе некоторых сердечно-сосудистых заболеваний

1.2.1 Артериальная гипертония.

1.2.4. Атеросклероз и сосудистое ремоделирование.

1.2.5 Клинические проявления дисфункции эндотелия.

1.3. Методы оценки функции эндотелия.

1.3.1. Оценка вазодилатирующей функции эндотелия.

1.3.2. Биохимические методы оценки NO-продуцирующей способности эндотелия.

1.4. Коррекция эндотелиальной функции.

1.4.1 Бета-адреноблокаторы.

ГЛАВА 2. МАТЕРИАЛЫ И МЕТОДЫ.

2.1. Материалы.

2.1.1. Критерии включения.

2.1.2 Критерии исключения.

2.1.3 Критерии прекращения.

2.1.4 Характеристика препаратов.

2.1.5. План исследования.

2.1.6. Оценка гипотензивной эффективности.

2.1.7. Оценка безопасности и переносимости.

2.2. Методы исследования на различных этапах.

2.2.1. Стандартный опрос.

2.2.2. Физикальное обследование с измерением массы тела, роста, АД.

2.2.3. Исследование ЭЗВД.

2.2.4. Определение липидного спектра и глюкозы.

2.2.5. Изучение стабильных метаболитов NO.

2.2.6. Критерии исключения из исследования на стабильные метаболиты

N02/N03:.

2.2.7 Изучение активности эндотелиальной NO - синтетазы.

2.3. Статистические методы анализа результатов.

ГЛАВА 3. РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЯ.

3.1. Антигипертензивная эфективность небиволола и метопролола.

3.2. Влияние небиволола и метопролола на маркеры эндотелиальной функции.

3.3. Сравнительная оценка маркеров эндотелиальной функции и АД в зависимости от изменения активности NOS в культуре клеток.

3.4 Влияние небиволола и метопролола на метаболические показатели трнспорта липидов и уровень глюкозы.

ГЛАВА 4. ОБСУЖДЕНИЕ.

ВЫВОДЫ.

Введение диссертации (часть автореферата) на тему «Антигипертензивная эффективность и влияние на маркеры эндотелиальной функции селективного бета-адреноблокатора небиволола у больных мягкой и умеренной артериальной гипертонией»

Актуальность темы:

Артериальная гипертония (АГ) остается одной из наиболее острых медико-социальных проблем современной медицины. Особенно актуальна эта проблема в России, где распространенность АГ достигает 40% [13].

В настоящее время общеизвестно, что при адекватном подборе доз все классы антигипертензивных препаратов обладают примерно одинаковым эффектом в плане снижения АД. Более того, крупные рандомизированные исследования не выявили преимущества препаратов какого-либо класса в плане предупреждения сердечно-сосудистых осложнений. В связи с этим все большее значение придается изучению других положительных эффектов антигипертензивных препаратов, не связанных с их основным* действием. Среди них важнейшее значение имеют метаболические эффекты, т.е. влияние препарата на эндогенные корригируемые факторы риска (ФР), которые довольно часто встречаются при АГ: нарушение липидного обмена, [8; 127, 128, 129], толерантности к глюкозе, инсулинорезистентность [63, 87, 210, 282,], нарушение в системе свертывания крови и фибринолиза [ 126,212, 214,232, 275]. Кроме того, за последние время, к требованиям, предъявляемым к антигипертензивным препаратам, к их метаболической нейтральности добавилась и способность корригировать дисфункцию эндотелия, которая довольно часто встречается при АГ. Объясняется это тем, что дисфункция эндотелия рассматривается в качестве раннего маркера атеротромбоза. Поэтому для обеспечения эффективной профилактики сердечно-сосудистых осложнений антигипертензивный препарат должен не только адекватно снижать АД, но и по возможности корригировать дисфункцию эндотелия.

Одним из важнейших маркеров дисфункции эндотелия является снижение выработки клетками эндотелия оксида азота (N0). В физиологических условиях N0 является не только мощным вазодилататором, но и тормозит пролиферацию ГМК, адгезию и агрегацию тромбоцитов, уменьшает окисление ЛНП и препятствует синтезу провоспалительных цитокинов. В последнее время появились сообщения о возможности коррекции дисфункции эндотелия с помощью антагонистов кальция [31, 32, 86, 86,159, 207, 304, 308] и ингибиторов АПФ [22,34, 66,68,77, 193,231].

Сравнительно недавно в клинической практике появился бета-адреноблокатор III поколения небиволол [69], имеющий высокоселективный характер воздействия на р(- рецепторы и прямое сосудорасширяющее воздействие, предположительно через увеличение синтеза N0 с помощью фермента eNOS. Проведенные исследования в этой области носили в основном экспериментальный характер

Таким образом, представляется актуальным провести комплексное сравнительное изучение антигипертензивного эффекта, влияния на макреры функции эндотелия и метаболические показатели транспорта липидов, что позволит объективно оценить возможности небиволола, как в плане снижения АД, так и в профилактике сердечно-сосудистых осложнений при АГ.

Цель исследования

Изучить антигипертензивное действие небиволола и оценить его влияние на маркеры эндотелиальной функции в сравнении с традиционно используемым бета-адреноблокатором, метопрололом, у больных мягкой и умеренной АГ и ФР ИБС.

Задачи исследования

1. Сравнить антигипертензивную эффективность небиволола и метопролола у больных мягкой и умеренной АГ и ФР ИБС.

2. Оценить динамику маркеров эндотелиальной функции:, ЭЗВД, активность eNOS в культуре клеток, уровень стабильных метаболитов NO у больных АГ при терапии небивололом и метопрололом.

3. Изучить влияние небиволола и метопролола на метаболические показатели транспорта липидов (уровень общего ХС, ХС ЛВП, ТГ), уровень глюкозы.

Научная новизна

Впервые проведено комплексное сравнительное исследование как антигипертензивной эффективности так и влияния на маркеры эндотелиальной функции двух селективных бета-адреноблокаторов небиволола и метопролола.

Установлено, что при сопоставимой антигипертензивной эффективности небиволол в отличие от метопролола улучшал эндотелиальную функцию. Это сопровождалось увеличением ЭЗВД, усилением активности eNOS в культуре эндотелиальных клеток, индуцируемой сывороткой крови больных после лечения, и повышением уровня стабильных метаболитов NO в сыворотке крови.

Практическая значимость

Результаты исследования обосновывают необходимость внедрения биохимического метода определения в сыворотке крови содержания стабильных метаболитов NO для более объективной оценки NO-продуцирующей функции эндотелия. Комплексное исследование антигипертензивного эффекта, влияния на маркеры эндотелиальной функции и метаболические показатели транспорта липидов и уровень глюкозы селективного бета-адреноблокатора небиволола позволило объективно оценить его возможности не только в плане контроля АД, но и предупреждения сердечно-сосудистых осложнений.

Заключение диссертации по теме «Кардиология», Спасская, Марианна Борисовна

2. Результаты исследования доказали необходимость внедрения биохимического метода определения в сыворотке крови стабильных метаболитов NO для более объективной оценки NO-продуцирующей функции эндотелия.

ПРАКТИЧЕСКИЕ РЕКОМЕНДАЦИИ

1. С целью адекватного контроля АД и улучшения состояния эндотелия рекомендовано более широкое применение небиволола в клинической практике у больных АГ и сопутствующими ФР ИБС.

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