Toblli Jorge Eduardo, DiGennaro Federico, Giani Jorge Fernando, Dominici Fernando Pablo
Hospital Aleman, Universidad de Buenos Aires, Buenos Aires, Argentina.
Vasc Health Risk Manag. 2012;8:151-60. doi: 10.2147/VHRM.S20669. Epub 2012 Mar 13.
Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/ nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care. Thus, nebivolol is an effective and well tolerated agent with benefits above those of traditional β-blockers due to its influence on nitric oxide release, which give it singular hemodynamic effects, cardioprotective activity, and a good tolerability profile. This paper reviews the pharmacology structure and properties of nebivolol, focusing on endothelial dysfunction, clinical utility, comparative efficacy, side effects, and quality of life in general with respect to the other antihypertensive agents.
内皮功能障碍是一种内皮的全身性病理状态,其特征是血管舒张剂(主要是一氧化氮)的生物利用度降低,导致内皮依赖性血管舒张受损,以及血管壁代谢和功能紊乱。内皮功能障碍的关键因素之一是活性氧的过度产生,其参与高血压、动脉粥样硬化、糖尿病、心脏肥大、心力衰竭、缺血再灌注损伤和中风的发展。由于内皮活性受损被认为在血管疾病、高血压和心力衰竭的病理生理学中起主要因果作用,因此改善这种状况的治疗药物具有临床意义。奈必洛尔是一种第三代β受体阻滞剂,对β1肾上腺素能受体具有高选择性,并通过与内皮L-精氨酸/一氧化氮途径相互作用引起血管舒张。这种双重作用机制突出了奈必洛尔的几种血流动力学特性,包括心率和血压降低以及收缩和舒张功能改善。尽管奈必洛尔降低血压的程度与传统β受体阻滞剂和其他类型的抗高血压药物相似,但它可能对难治性高血压患者具有优势,例如伴有糖尿病和肥胖等其他合并症的心力衰竭患者,以及一氧化氮介导的内皮功能障碍可能更明显的老年患者。此外,最近的数据表明,与标准治疗相比,奈必洛尔似乎是老年心力衰竭患者的一种具有成本效益的治疗方法。因此,奈必洛尔是一种有效且耐受性良好的药物,由于其对一氧化氮释放的影响,具有优于传统β受体阻滞剂的益处,使其具有独特的血流动力学效应、心脏保护活性和良好的耐受性。本文综述了奈必洛尔的药理结构和特性,重点关注内皮功能障碍、临床应用、比较疗效、副作用以及与其他抗高血压药物相比的总体生活质量。