Gupta Sandeep, Wright Harold M
Department of Pharmacology, Forest Research Institute, Jersey City, NJ 07311, USA.
Cardiovasc Ther. 2008 Fall;26(3):189-202. doi: 10.1111/j.1755-5922.2008.00054.x.
Nebivolol (Bystolic) is a cardioselective beta 1 (beta(1))-adrenergic receptor blocker with endothelium-dependent vasodilating properties. The endothelium-dependent relaxation induced by nebivolol is blocked by inhibitors of nitric oxide synthase (NOS) and guanylate cyclase. Nebivolol also increases in vitro and in vivo nitric oxide (NO), which is an essential signaling molecule involved in the maintenance of cardiovascular homeostasis. This review summarizes the data involving nebivolol and NO bioavailability. Endothelium-dependent relaxation of blood vessels, which is impaired in hypertensive animals and humans, is reversed by nebivolol treatment. Animals exhibiting endothelial dysfunction also show an improvement in NO-cyclic guanosine monophosphate (cGMP) signaling and an increase in NO bioavailability when treated with nebivolol. When blood vessel and cultured endothelial cells from hypertensive animals are treated with nebivolol, there is a decrease in superoxide production and an increase in the expression and activity of endothelial NOS (eNOS). As a result of the increased bioavailability of NO, nebivolol also increases in vivo arterial distensibility, glomerular filtration rate, and renal plasma flow. In normotensive volunteers, nebivolol infusion increases the forearm blood flow, an effect that is blocked by inhibitors of NOS and restored by the NOS substrate, L-arginine. In hypertensive patients, chronic treatment with nebivolol improves endothelium-dependent vasodilation induced by acetylcholine and shear stress and reverses endothelium-dependent vasoconstriction. Furthermore, nebivolol displays distinct hemodynamic properties in patients that include improvements in stroke volume and a decrease in peripheral vascular resistance. These studies demonstrate that nebivolol produces endothelium-dependent vasodilation by increasing NO release, decreasing oxidative stress to increase NO bioavailability, or both. The NO-dependent vasodilatory action of nebivolol, coupled with its high beta(1)-adrenergic receptor selectivity, is unique among the clinically available beta-blockers and contributes to its efficacy and improved tolerability (e.g., less fatigue and sexual dysfunction) as an antihypertensive agent.
奈必洛尔（Bystolic）是一种具有内皮依赖性血管舒张特性的心脏选择性β1（β₁）-肾上腺素能受体阻滞剂。奈必洛尔诱导的内皮依赖性舒张作用被一氧化氮合酶（NOS）抑制剂和鸟苷酸环化酶抑制剂所阻断。奈必洛尔还能在体外和体内增加一氧化氮（NO），而NO是维持心血管稳态所必需的信号分子。本综述总结了有关奈必洛尔和NO生物利用度的数据。在高血压动物和人类中受损的血管内皮依赖性舒张作用，可通过奈必洛尔治疗得到逆转。表现出内皮功能障碍的动物在用奈必洛尔治疗后，NO-环磷酸鸟苷（cGMP）信号传导也有所改善，且NO生物利用度增加。当用奈必洛尔处理高血压动物的血管和培养的内皮细胞时，超氧化物生成减少，内皮型一氧化氮合酶（eNOS）的表达和活性增加。由于NO生物利用度增加，奈必洛尔还能增加体内动脉扩张性、肾小球滤过率和肾血浆流量。在血压正常的志愿者中，输注奈必洛尔可增加前臂血流量，该作用被NOS抑制剂阻断，并被NOS底物L-精氨酸恢复。在高血压患者中，奈必洛尔的长期治疗可改善乙酰胆碱和剪切应力诱导的内皮依赖性血管舒张，并逆转内皮依赖性血管收缩。此外，奈必洛尔在患者中表现出独特的血流动力学特性，包括心搏量增加和外周血管阻力降低。这些研究表明，奈必洛尔通过增加NO释放、降低氧化应激以增加NO生物利用度或两者兼而有之，从而产生内皮依赖性血管舒张作用。奈必洛尔的NO依赖性血管舒张作用，及其高度的β₁-肾上腺素能受体选择性，在临床可用的β受体阻滞剂中是独一无二的，这有助于其作为抗高血压药物的疗效和更好的耐受性（如较少的疲劳和性功能障碍）。
