拉洛西芬通过减少氧化应激和增强氧化生产来改善高血压中的内皮功能障碍
Sven Wassmann1, Ulrich Laufs, Djordje Stamenkovic
1Medizinische Klinik und Poliklinik, Innere Medizin III, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
Circulation
|May 1, 2002
概括
选择性雌激素受体调节剂 (如拉洛西芬) 通过增加氧化的可用性和减少血管中的氧化应激来改善血压. 这些发现表明,拉洛西芬具有血管保护作用,对高血压有益.
科学领域:
- 心血管药理学心血管药理学
- 内分泌学 在内分泌学.
- 血管生物学 血管生物学
背景情况:
- 与雌激素相比,选择性雌激素受体调节剂 (SERM) 的血管保护潜力,如拉洛西芬,仍然不完全理解.
- 澄清SERM对血管的影响对于理解其治疗应用至关重要.
研究的目的:
- 为了研究拉洛西芬在雄性自发高血压大鼠的血管效应.
- 为了确定拉洛西芬是否可以改善高血压诱导的内皮功能障碍.
主要方法:
- 雄性自发高血压大鼠和Wistar大鼠被用拉洛西芬 (10 mg/kg/天) 或载体治疗了10周.
- 评估了血管反应性,氧化 (NO) 生产和NADPH氧化酶活性.
- 研究了在培养细胞中对活性氧物种 (ROS) 生产的影响.
主要成果:
- 拉洛西芬改善了内皮依赖的血管扩张,并通过增强内皮NO合成酶 (eNOS) 活性增加了NO的生物可用性.
- 它减少了超氧化物产生,并降低了血管rac1的活性/表达,这是NAD(P) H氧化酶的关键组成部分.
- 在用拉洛西芬治疗的高血压大鼠中观察到显著的血压降低.
结论:
- 拉洛西芬治疗通过增加NO生物可用性,有效地改善高血压中的内皮功能障碍.
- 这是由增强的eNOS活性和依赖于雌激素受体的降低血管ROS生产的介导.
- 这些血管改善导致血压显著降低,血管损伤减少.
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