Molecular and Clinical Pharmacology Program, Faculty of Medicine, Biomedical Sciences Institute, Universidad de Chile, Santiago, Chile.
Basic Clin Pharmacol Toxicol. 2012 Nov;111(5):309-16. doi: 10.1111/j.1742-7843.2012.00911.x. Epub 2012 Jul 14.
Oxidative stress and endothelial dysfunction have been associated with essential hypertension (EH) mechanisms. The purpose of this study was to evaluate the effect of carvedilol and nebivolol on the oxidative stress-related parameters and endothelial function in patients with EH. The studied population included 57 patients, either sex, between 30 and 75 years of age, with mild-to-moderate EH complications. Participants were randomized to receive either carvedilol (12.5 mg) (n = 23) or nebivolol (5 mg) (n = 21) for 12 weeks. Measurements included; 24-hr ambulatory blood pressure (BP), flow-mediated dilatation, levels of nitric oxide estimated as nitrite - a nitric oxide metabolite ( NO₂) - in plasma, and oxidative stress-related parameters in plasma and erythrocyte. EH patients who were treated with nebivolol or carvedilol showed systolic BP reductions of 17.4 and 19.9 mmHg, respectively, compared with baseline values (p < 0.01). Diastolic BP was reduced by 13.7 and 12.8 mmHg after the treatment with ebivolol and carvedilol, respectively (p < 0.01) (fig. 2B). Nebivolol and carvedilol showed 7.3% and 8.1% higher endothelium-dependent dilatation in relation to baseline values (p < 0.05). Ferric-reducing ability of plasma (FRAP) and reduced glutathione/oxidized glutathione (GSSH) ratio showed 31.5% and 29.6% higher levels in the carvedilol group compared with basal values; however, nebivolol-treated patients did not show significant differences after treatment. On the other hand, the NO₂ plasma concentration was not modified by the administration of carvedilol. However, nebivolol enhanced these levels in 62.1% after the treatment. In conclusion, this study demonstrated the antihypertensive effect of both beta-blockers. However, carvedilol could mediate these effects by an increase in antioxidant capacity and nebivolol through the raise in NO₂ concentration. Further studies are needed to determine the molecular mechanism of these effects.
氧化应激和内皮功能障碍与原发性高血压(EH)的机制有关。本研究的目的是评估卡维地洛和奈必洛尔对 EH 患者氧化应激相关参数和内皮功能的影响。研究人群包括 57 名年龄在 30 至 75 岁之间的男女患者,患有轻度至中度 EH 并发症。参与者被随机分为两组,分别接受卡维地洛(12.5mg)(n=23)或奈必洛尔(5mg)(n=21)治疗 12 周。测量包括:24 小时动态血压(BP)、血流介导的扩张、血浆中估计的作为一氧化氮代谢物(NO₂)的硝酸盐水平、以及血浆和红细胞中的氧化应激相关参数。与基线值相比,接受奈必洛尔或卡维地洛治疗的 EH 患者的收缩压分别降低了 17.4 和 19.9mmHg(p<0.01)。接受奈必洛尔和卡维地洛治疗后,舒张压分别降低了 13.7 和 12.8mmHg(p<0.01)(图 2B)。奈必洛尔和卡维地洛显示内皮依赖性扩张分别比基线值高 7.3%和 8.1%(p<0.05)。与基线值相比,血浆铁还原能力(FRAP)和还原型谷胱甘肽/氧化型谷胱甘肽(GSSH)比值分别升高 31.5%和 29.6%;然而,奈必洛尔治疗的患者在治疗后没有显示出显著差异。另一方面,卡维地洛的给药并没有改变血浆中的 NO₂浓度。然而,奈必洛尔在治疗后使这些水平提高了 62.1%。总之,本研究表明了两种β受体阻滞剂的降压作用。然而,卡维地洛可以通过增加抗氧化能力来介导这些作用,而奈必洛尔则可以通过提高 NO₂浓度来介导这些作用。需要进一步的研究来确定这些作用的分子机制。