Nebivolol Promising Option for Management of Pulmonary Hypertension | Journal Scan

Study Questions:

Does nebivolol, a β1 antagonist and β2,3-agonist improve pulmonary arterial hypertension (PAH) in an experimental model, and reverse the PAH-related phenotype of pulmonary endothelial cells (P-EC)?

Methods:

The effects of nebivolol were compared with metoprolol, a first-generation β1-selective beta-blocker, on human cultured PAH and control P-EC proliferation, vasoactive, and proinflammatory factor production and crosstalk with PA smooth cells (PASMCs), and on norepinephrine precontracted PA rings. Additionally, the effect of the beta-blockers was assessed in the rat monocrotaline-induced experimental model of PAH.

Results:

PAH P-EC overexpressed the proinflammatory mediators interleukin-6, monocyte chemoattractant protein-1, fibroblast growth factor-2, and the potent vasoconstrictive agent endothelin-1, as compared to control cells. This pathological phenotype was corrected by nebivolol but not metoprolol in a dose-dependent fashion. PAH P-EC proliferates more than control cells, and stimulate more PASMC mitosis, a growth abnormality which was normalized by nebivolol but not by metoprolol. Nebivolol but not metoprolol induced an endothelium- and nitric oxide dependant relaxation of PA. Nebivolol was also more potent than metoprolol in improving cardiac function, pulmonary vascular remodeling and inflammation of rats with PAH.

Conclusions:

Nebivolol could be a promising option for the management of PAH, improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function. Until clinical studies are undertaken, however, routine use of beta-blockers in PAH cannot be recommended.

Perspective:

Much progress has been made in treatment with PAH-specific drugs, but that a beta-blocker with an excellent safety profile might reduce the rate of progression and improve right ventricular function in a universally fatal disease is more than exciting.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Hypertension, Heart Failure, Pulmonary Artery, Ventricular Dysfunction, Right, Ventricular Function, Right, Ventricular Remodeling, Models, Theoretical, Metoprolol, Inflammation, Endothelial Cells, Adrenergic beta-Antagonists, Interleukin-6, Norepinephrine, Phenotype


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