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比索洛尔与美托洛尔对高血压西班牙裔绝经后女性钠敏感性和肾脏钠处理的影响。

Effects of nebivolol versus metoprolol on sodium sensitivity and renal sodium handling in hypertensive Hispanic postmenopausal women.

出版信息

Hypertension. 2014 Aug;64(2):287-95. doi: 10.1161/HYPERTENSIONAHA.114.03476.

Abstract

Several consistent lines of evidence indicate an association between sodium sensitivity and impaired nitric oxide bioactivity. Nevertheless, whether restoring nitric oxide in humans by pharmacological means can ameliorate sodium sensitivity has not been investigated. Because nebivolol has been demonstrated to increase nitric oxide bioactivity in both laboratory and clinical investigations, we hypothesized that nebivolol might ameliorate sodium sensitivity and improve renal sodium handling in comparison to metoprolol. We therefore conducted a randomized, 2-treatment-period crossover trial in 19 Hispanic postmenopausal women with hypertension to determine the comparative effects of nebivolol versus metoprolol on (1) 24-hour ambulatory blood pressure response to an increase in dietary sodium from 5 days of low sodium to 5 days of high sodium, (2) renal natriuretic response to a 1-L saline challenge, and (3) asymmetrical dimethylarginine. Clinic blood pressure and heart rate were significantly reduced after 4 weeks of treatment with both nebivolol and metoprolol. Twenty-four–hour mean systolic blood pressure increased sharply from low sodium to high sodium for both nebivolol and metoprolol. Nevertheless, the increases in blood pressure did not differ between the 2 drugs: 7.7 (3.1, 12.3) mm Hg with metoprolol and 9.3 (4.6, 13.9) mm Hg with nebivolol (P=0.63). Furthermore, we observed no differences between the drugs in natriuretic response to saline challenge or asymmetrical dimethylarginine. In a sodium-sensitive population, at doses sufficient to produce reductions in blood pressure and heart rate, nebivolol did not demonstrate a significant effect on sodium sensitivity or sodium handling compared with metoprolol.

摘要

有几项确凿的证据表明,钠敏感性与一氧化氮生物活性受损之间存在关联。然而,通过药理学手段恢复人体中的一氧化氮是否能改善钠敏感性尚未得到研究。由于在实验室和临床研究中已经证实比索洛尔能增加一氧化氮的生物活性,因此我们假设与美托洛尔相比,比索洛尔可能会改善钠敏感性并改善肾脏对钠的处理。因此,我们在 19 名患有高血压的西班牙绝经后女性中进行了一项随机、2 期交叉试验,以确定比索洛尔与美托洛尔对以下方面的比较效果:(1)从低钠饮食的 5 天增加到高钠饮食的 5 天期间,24 小时动态血压对膳食钠增加的反应;(2)生理盐水 1 升冲击试验的肾脏利钠反应;和(3)不对称二甲基精氨酸。服用比索洛尔和美托洛尔治疗 4 周后,诊室血压和心率均显著降低。24 小时平均收缩压在低钠饮食和高钠饮食之间均急剧升高。然而,这两种药物之间血压升高没有差异:美托洛尔组为 7.7(3.1,12.3)mmHg,比索洛尔组为 9.3(4.6,13.9)mmHg(P=0.63)。此外,我们观察到在生理盐水冲击试验或不对称二甲基精氨酸方面,两种药物之间没有差异。在钠敏感人群中,在足以降低血压和心率的剂量下,与美托洛尔相比,比索洛尔对钠敏感性或钠处理没有显著影响。

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