Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans.
Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans.
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DOI：
10.1161/hypertensionaha.113.01302
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Vongpatanasin W
中科院分区：
文献类型：
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作者：
Price A;Raheja P;Wang Z;Arbique D;Adams-Huet B;Mitchell JH;Victor RG;Thomas GD;Vongpatanasin W
在年轻健康的人类中，交感神经血管收缩在运动期间明显减弱，以优化流向代谢活跃肌肉的血流。这种被称为功能性交感神经溶解的现象在高血压人类和大鼠中通过涉及氧化应激和一氧化氮（NO）失活的血管紧张素II依赖性机制受损。奈必洛尔是一种β1−肾上腺素能受体阻滞剂，具有NO依赖性血管舒张和抗氧化特性。因此，我们询问奈必洛尔是否可以恢复高血压患者的功能性交感神经松解。在21例I期高血压受试者中，我们采用双盲交叉设计，在基线、奈必洛尔（5-20 mg/d）或美托洛尔（100-300 mg/d）治疗12周后，测量了静息时和节律性握力运动期间下体负压（LBNP）诱发的交感神经活动（SNA）反射增加的肌肉氧合和前臂血流（FBF）反应。我们发现奈必洛尔对LBNP诱导的静息前臂氧合和FBF降低没有影响（分别从−29±5至−30±5%和从−29±3至−29± 3%; p=NS）。然而，奈必洛尔减弱了LBNP诱导的运动前臂氧合和FBF降低（分别从−14±4%降至−1±5%和从−15 ±2%降至−6± 2%，均p < 0.05）。奈必洛尔对前臂运动时氧合和FBF的影响与美托洛尔在相同受试者中的作用相似，尽管血压降低相似。奈必洛尔对休息时或握持期间的SNA没有影响，表明对血管功能有直接影响。因此，我们的数据表明奈必洛尔通过不涉及β1-肾上腺素能受体的机制恢复高血压患者的功能性交感神经溶解。
In young healthy humans, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis is impaired in hypertensive humans and rats by angiotensin II-dependent mechanisms involving oxidative stress and inactivation of nitric oxide (NO). Nebivolol is a β1−adrenergic receptor blocker that has NO-dependent vasodilatory and antioxidant properties. We therefore asked if nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage I hypertension, we measured muscle oxygenation and forearm blood flow (FBF) responses to reflex increases in sympathetic nerve activity (SNA) evoked by lower body negative pressure (LBNP) at rest and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5–20 mg/day), or metoprolol (100–300 mg/day), using a double-blind crossover design. We found that nebivolol had no effect on LBNP-induced decreases in oxygenation and FBF in resting forearm (from −29±5 to −30±5% and from −29±3 to −29±3%, respectively; p=NS). However, nebivolol attenuated the LBNP-induced reduction in oxygenation and FBF in exercising forearm (from −14±4% to −1±5% and from −15 ±2% to −6±2%, respectively, both p < 0.05). This effect of nebivolol on oxygenation and FBF in exercising forearm was not observed with metoprolol in the same subjects despite a similar reduction in BP. Nebivolol had no effect on SNA at rest or during handgrip, suggesting a direct effect on vascular function. Thus, our data demonstrate that nebivolol restored functional sympatholysis in hypertensive humans by a mechanism that does not involve β1-adrenergic receptors.