（英文原文）Nebivolol for Improving Endothelial Dysfunction, Pulmonary VascularRemodeling, and Right Heart Function in Pulmonary Hypertension
Background Endothelial cell (EC) dysfunction plays a central role in thepathogenesis of pulmonary arterial hypertension (PAH), promotingvasoconstriction, smooth muscle proliferation, and inflammation.
Objectives This study sought to test the hypothesis that nebivolol, aβ1-antagonist and β2,3-agonist, may improve PAH and reverse the PAH-relatedphenotype of pulmonary ECs (P-EC).
Methods We compared the effects of nebivolol with metoprolol, afirst-generation β1-selective β-blocker, on human cultured PAH and control P-ECproliferation, vasoactive and proinflammatory factor production, and crosstalkwith PA smooth muscle cells. We assessed the effects of both β-blockers inprecontracted PA rings. We also compared the effects of both β-blockers inexperimental PAH.
Results PAH P-ECs overexpressed the proinflammatory mediatorsinterleukin-6 and monocyte chemoattractant protein-1,fibroblast growth factor-2, and the potent vasoconstrictive agentendothelin-1 as compared with control cells. This pathological phenotype wascorrected by nebivolol but not metoprolol in a dose-dependent fashion. Weconfirmed that PAH P-EC proliferate more than control cells and stimulate morePA smooth muscle cell mitosis, a growth abnormality that was normalized bynebivolol but not by metoprolol. Nebivolol but not metoprolol inducedendothelium-dependent and nitric oxide–dependent relaxation of PA. Nebivololwas more potent than metoprolol in improving cardiac function, pulmonaryvascular remodeling, and inflammation of rats with monocrotaline-inducedpulmonary hypertension.
Conclusions Nebivolol could be a promising option for the management ofPAH, improving endothelial dysfunction, pulmonary vascular remodeling, andright heart function. Until clinical studies are undertaken, however, routineuse of β-blockers in PAH cannot be recommended.
來源：CardioSource Journal scans（February 18，2015）
奈必洛爾或有望治療肺動脈高壓
近日一項研究顯示，奈必洛爾或有望治療肺動脈高壓（PAH），改善內皮功能障礙、肺血管重構以及右心功能。然而，在進行臨床試驗以前，不建議常規使用β-阻滯劑治療PAH。
內皮細胞（EC）功能障礙在PAH的發病機制中具有重要作用，其可促進血管收縮、平滑肌增生並引發炎症。本研究旨在驗證奈必洛爾可能改善PAH並逆轉PAH相關肺EC表型（P-EC）的假說，比較奈必洛爾和美託洛爾對人培養PAH和對照P-EC增殖、血管、促炎因子生成以及肺動脈平滑肌細胞串擾的作用。
結果顯示，與對照細胞相比，PAH P-EC過度表達促炎介質白介素-6和單核細胞化學引誘物蛋白-1、成纖維細胞生長因子-2以及強效血管收縮物內皮素-1。奈必洛爾可修正這種病理表型但美託洛爾不能。研究證實PAH P-EC增殖超過了對照細胞，並可刺激更多的肺動脈平滑肌細胞有絲分裂（一種生長異常，奈必洛爾可以使之恢復正常，而美託洛爾不行）。在改善野百合鹼誘導的PAH小鼠心功能、肺血管重構以及炎症方面，奈必洛爾比美託洛爾更強效。