Maffei Angelo, Lembo Giuseppe
Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli (IS), Italy.
Ther Adv Cardiovasc Dis. 2009 Aug;3(4):317-27. doi: 10.1177/1753944709104496. Epub 2009 May 14.
beta-blockers are among the most widely used drugs in the prevention and treatment of cardiovascular disease, although they are associated with increased peripheral resistance. Third-generation beta-blockers avoid this adverse effect by inducing vasodilation through different mechanisms. In particular, nebivolol, a highly selective blocker of beta(1)-adrenergic receptors, is the only beta-blocker known to induce vascular production of nitric oxide, the main endothelial vasodilator. The specific mechanism of nebivolol is particularly relevant in hypertension, where nitric oxide dysfunction occurs. Indeed, nebivolol is able to reverse endothelial dysfunction. Nebivolol induces nitric oxide production via activation of beta(3)-adrenergic receptors, which can explain the good metabolic profile observed after treatment with this drug. Moreover, nebivolol can also stimulate the beta(3)-adrenergic receptor-mediated production of nitric oxide in the heart, and this stimulation can result in a greater protection against heart failure. In conclusion, nebivolol has a unique profile among antihypertensive drugs, adding to a very high selectivity against beta(1) adrenergic receptors, and an agonist action on beta(3) receptors and nitric oxide (NO), which has led to clinically significant improvements in hypertensive patients.
β受体阻滞剂是预防和治疗心血管疾病中使用最广泛的药物之一，尽管它们与外周阻力增加有关。第三代β受体阻滞剂通过不同机制诱导血管舒张来避免这种不良反应。特别是奈必洛尔，一种高度选择性的β₁肾上腺素能受体阻滞剂，是已知唯一能诱导血管产生一氧化氮（主要的内皮血管舒张剂）的β受体阻滞剂。奈必洛尔的具体机制在一氧化氮功能障碍发生的高血压中尤为重要。事实上，奈必洛尔能够逆转内皮功能障碍。奈必洛尔通过激活β₃肾上腺素能受体诱导一氧化氮生成，这可以解释使用该药物治疗后观察到的良好代谢特征。此外，奈必洛尔还可以刺激心脏中β₃肾上腺素能受体介导的一氧化氮生成，这种刺激可以增强对心力衰竭的保护作用。总之，奈必洛尔在抗高血压药物中具有独特的特性，除了对β₁肾上腺素能受体具有很高的选择性外，还对β₃受体和一氧化氮（NO）具有激动作用，这已使高血压患者在临床上有显著改善。
