PT  - JOURNAL ARTICLE
AU  - Frederic Perros
AU  - Sana Bentebbal
AU  - Benoit Ranchoux
AU  - Peter Dorfmüller
AU  - Florence Lecerf
AU  - Elie Fadel
AU  - Gerald Simonneau
AU  - Marc Humbert
AU  - Harm Jan Bogaard
AU  - Saadia Eddahibi
TI  - Nebivolol and pulmonary hypertension
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P317
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P317.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P317.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - BackgroundEndothelial cell (EC) dysfunction is a key mechanism in pulmonary arterial hypertension (PAH) pathogenesis by promoting smooth muscle proliferation, vasoconstriction and inflammation.AimTo demonstrate that nebivolol may improve PAH.MethodsWe studied the effects of nebivolol (β1 antagonist and β2-3 agonist) compared to metoprolol (first generation β1-selective β-blocker) on cultured PAH and control pulmonary artery (PA) EC (PAEC), proliferation, proinflammatory and vasoactive factors production and on crosstalk with PA smooth cells (PASMC). We compared the effects of nebivolol and metoprolol in precontracted PA rings and in pulmonary hypertension (PH) model (monocrotaline [MCT]-exposed rat).ResultsPAH PAEC overexpressed the proinflammatory mediators IL-6 and MCP-1, the growth factor FGF2, and the potent vasoconstrictive agent endothelin-1 as compared to control PAEC. Nebivolol treatment corrected this pathological phenotype in a dose-dependent way whereas metoprolol did not. We also confirmed that PAH PAEC proliferate more than control cells, and stimulate more PASMC mitosis. This growth abnormality was regulated by nebivolol but not by metoprolol. Contrary to metoprolol, Nebivolol also induced an endothelium- and nitric oxide-dependant relaxation of PA. Finally, nebivolol was more efficient than metoprolol in improving survival, cardiac function, pulmonary vascular remodeling and inflammation of rats with MCT-induced PH.ConclusionsOur work demonstrates for the first time that nebivolol improves endothelial dysfunction, pulmonary vascular remodeling, and right heart function and could be a safe option for the management of PAH. Until clinical studies are undertaken, however, routine use of beta-blockers in PAH cannot be recommended.