Cockcroft J R, Chowienczyk P J, Brett S E, Chen C P, Dupont A G, Van Nueten L, Wooding S J, Ritter J M
Department of Clinical Pharmacology, United Medical School, Guy's Hospital, London, England.
J Pharmacol Exp Ther. 1995 Sep;274(3):1067-71.
Nebivolol, a beta 1 selective adrenergic receptor antagonist with additional properties, is a racemic mixture of (S,R,R,R)- and (R,S,S,S)-enantiomers. We investigated its effects on human forearm vasculature. Blood flow was measured using venous occlusion plethysmography during brachial artery infusion of drugs. Interaction between nebivolol and the L-arginine/nitric oxide pathway was investigated via comparison with carbachol (an endothelium-dependent agonist) and nitroprusside, and by coinfusion of a competitive inhibitor of nitric oxide synthase, NG-monomethyl L-arginine (LNMMA) +/- L-arginine. Nebivolol (354 micrograms/min) increased blood flow by 91 +/- 18% (mean +/- SEM, n = 8, P < .01) whereas an equimolar dose of atenolol had no significant effect. L-NMMA (1 mg/min) inhibited vasodilation to nebivolol (by 65 +/- 10%) and carbachol (by 49 +/- 8%) to a significantly greater extent than it reduced responses to nitroprusside. Inhibition of nebivolol response by L-NMMA was abolished by L-arginine (62 +/- 11% inhibition by L-NMMA, 15 +/- 17% inhibition by L-NMMA with L-arginine, 10 mg/min, n = 8). Vasodilation caused by the (S,R,R,R)- and (R,S,S,S)-enantiomers was similar. We conclude that nebivolol vasodilates human forearm vasculature via the L-arginine/nitric oxide pathway.
奈必洛尔是一种具有其他特性的β1选择性肾上腺素能受体拮抗剂，是（S，R，R，R）-和（R，S，S，S）-对映体的外消旋混合物。我们研究了其对人体前臂血管系统的影响。在肱动脉输注药物期间，使用静脉闭塞体积描记法测量血流量。通过与卡巴胆碱（一种内皮依赖性激动剂）和硝普钠比较，并通过共同输注一氧化氮合酶的竞争性抑制剂NG-单甲基L-精氨酸（LNMMA）+/-L-精氨酸，研究了奈必洛尔与L-精氨酸/一氧化氮途径之间的相互作用。奈必洛尔（354微克/分钟）使血流量增加了91±18%（平均值±标准误，n = 8，P <.01），而等摩尔剂量的阿替洛尔则无显著影响。L-NMMA（1毫克/分钟）对奈必洛尔（65±10%）和卡巴胆碱（49±8%）的血管舒张抑制作用明显大于对硝普钠反应的降低程度。L-精氨酸消除了L-NMMA对奈必洛尔反应的抑制作用（L-NMMA抑制62±11%，L-NMMA与L-精氨酸共同作用抑制15±17%，L-精氨酸10毫克/分钟，n = 8）。（S，R，R，R）-和（R，S，S，S）-对映体引起的血管舒张作用相似。我们得出结论，奈必洛尔通过L-精氨酸/一氧化氮途径使人体前臂血管舒张。
