Fratta Pasini Anna, Garbin Ulisse, Nava Maria Cristina, Stranieri Chiara, Davoli Anna, Sawamura Tatsuya, Lo Cascio Vincenzo, Cominacini Luciano
Department of Biomedical and Surgical Sciences (Medicina D), University of Verona, Verona, Italy.
J Hypertens. 2005 Mar;23(3):589-96. doi: 10.1097/01.hjh.0000160216.86597.ff.
To obtain further insight into the mechanism underlying the vasodilator effect of nebivolol. Since oxidative inactivation of nitric oxide (NO) is regarded as an important cause of its decreased biological activity, we studied (1) the effect of nebivolol on some oxidative parameters in essential hypertensive patients; (2) the effect of plasma of nebivolol-treated patients on reactive oxygen species production and NO availability in endothelial cells.
A total of 20 healthy subjects and 20 matched essential hypertensive patients treated with atenolol or nebivolol according to a double-blind, randomized design participated in the study. We measured low-density lipoprotein (LDL) and plasma hydroperoxides, 8-isoprostanes, oxidized LDL, susceptibility of LDL to oxidation (lag phase) and LDL vitamin E and the effect of plasma of nebivolol- and atenolol-treated patients on reactive oxygen species production and NO availability in endothelial cells exposed to oxidative stress.
In hypertensive patients, nebivolol and atenolol significantly reduced blood pressure values after 4 weeks of treatment. Plasma and LDL hydroperoxides, plasma 8-isoprostanes, plasma ox-LDL and LDL lag phase were significantly improved only in the patients receiving nebivolol compared with the atenolol group. Similarly there was a reduction of reactive oxygen species (ROS) and O2*- concentration in endothelial cells exposed to oxidative stress after incubation of the cells with plasma of the patients enrolled in the trial only in the patients receiving nebivolol compared to atenolol group. Furthermore, the reduction of basal and stimulated NO induced by oxidative stress in endothelial cells was significantly lower in the patients receiving nebivolol compared to atenolol group.
The findings of the present study indicate that nebivolol, through its antioxidant properties, increases NO also by decreasing its oxidative inactivation.
进一步深入了解奈必洛尔血管舒张作用的潜在机制。由于一氧化氮（NO）的氧化失活被认为是其生物活性降低的重要原因，我们研究了：（1）奈必洛尔对原发性高血压患者某些氧化参数的影响；（2）奈必洛尔治疗患者的血浆对内皮细胞中活性氧生成和NO可用性的影响。
按照双盲、随机设计，共有20名健康受试者以及20名匹配的接受阿替洛尔或奈必洛尔治疗的原发性高血压患者参与了本研究。我们测量了低密度脂蛋白（LDL）和血浆氢过氧化物、8-异前列腺素、氧化型LDL、LDL的氧化敏感性（滞后期）以及LDL维生素E，还研究了奈必洛尔和阿替洛尔治疗患者的血浆对暴露于氧化应激的内皮细胞中活性氧生成和NO可用性的影响。
在高血压患者中，治疗4周后，奈必洛尔和阿替洛尔均显著降低了血压值。与阿替洛尔组相比，仅接受奈必洛尔治疗的患者血浆和LDL氢过氧化物、血浆8-异前列腺素、血浆氧化型LDL以及LDL滞后期均有显著改善。同样，与阿替洛尔组相比，仅在接受奈必洛尔治疗的患者中，将试验患者的血浆与内皮细胞孵育后，暴露于氧化应激的内皮细胞中的活性氧（ROS）和超氧阴离子（O2*-）浓度降低。此外，与阿替洛尔组相比，接受奈必洛尔治疗的患者中氧化应激诱导的内皮细胞基础NO和刺激后NO的降低幅度明显更小。
本研究结果表明，奈必洛尔通过其抗氧化特性，还通过减少NO的氧化失活来增加NO。
