Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO
Department of Medicine, University of Colorado Denver, Aurora, CO.
J Am Heart Assoc. 2017 Nov 9;6(11):e007437. doi: 10.1161/JAHA.117.007437.
Vascular endothelial fibrinolytic function is impaired in adults with prehypertension and hypertension and plays a mechanistic role in the development of atherothrombotic events. The influence of β-blockers on endothelial fibrinolysis is unknown. This study compared the effects of chronic nebivolol and metoprolol treatment on endothelial tissue-type plasminogen activator (t-PA) release in adults with elevated blood pressure (BP).
Forty-four middle-aged adults (36% women) with elevated BP completed a 3-month, double-blind, randomized, placebo-controlled trial comparing nebivolol (5 mg/d), metoprolol succinate (100 mg/d), and placebo. Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside before and after each intervention. In a subset, the dose-response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C. At baseline, resting BP and endothelial t-PA release were comparable between the 3 groups. BP decreased to a similar extent (≈10 mm Hg) in the nebivolol- and metoprolol-treated groups. There was a substantial increase (≈30%; <0.05) in the capacity of the endothelium to release t-PA following chronic treatment with nebivolol but not metoprolol or placebo. Mitigating oxidant stress with vitamin C coinfusion potentiated t-PA release (90%; <0.05) at baseline in all groups. However, after the intervention, t-PA release was unchanged by vitamin C coinfusion in the nebivolol group only.
Nebivolol but not metoprolol improves endothelial t-PA release in adults with elevated BP. This may be an important vascular benefit of nebivolol.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01595516.
血管内皮纤维蛋白溶解功能在患有高血压前期和高血压的成年人中受损，并在动脉血栓栓塞事件的发展中起机械作用。β受体阻滞剂对内皮纤维蛋白溶解的影响尚不清楚。本研究比较了慢性 nebivolol 和 metoprolol 治疗对血压升高的成年人内皮组织型纤溶酶原激活物（t-PA）释放的影响。
44 名中年高血压患者（36%为女性）完成了为期 3 个月的、双盲、随机、安慰剂对照试验，比较了 nebivolol（5mg/d）、琥珀酸美托洛尔（100mg/d）和安慰剂。在每次干预前后，通过肱动脉内输注缓激肽和硝普钠，在体内测定净内皮 t-PA 释放。在亚组中，通过与抗氧化维生素 C 共输注重复了缓激肽和硝普钠的剂量反应曲线。在基线时，3 组之间的静息血压和内皮 t-PA 释放相似。nebivolol 和 metoprolol 治疗组的血压均降低至相似程度（≈10mmHg）。与 nebivolol 慢性治疗相比，内皮释放 t-PA 的能力有显著增加（≈30%；<0.05），但 metoprolol 或安慰剂无变化。用维生素 C 共输注减轻氧化应激在所有组中均使基线 t-PA 释放增加（90%；<0.05）。然而，在干预后，只有在 nebivolol 组中，维生素 C 共输注对 t-PA 释放没有影响。
与 metoprolol 相比，nebivolol 可改善高血压患者的内皮 t-PA 释放。这可能是 nebivolol 的一个重要血管益处。
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