0123 : Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension

Autor: Saadia Eddahibi, Gérald Simonneau, Philippe Jourdon, Chris Happé, Sana Bentebbal, Harm Jan Bogaard, Benoit Ranchoux, Elie Fadel, Florence Lecerf, Marc Humbert, Fabrice Antigny, Peter Dorfmüller, Mohamed Izikki, Frédéric Perros
Rok vydání: 2015
Předmět:
Zdroj: Archives of Cardiovascular Diseases Supplements. 7(2)
ISSN: 1878-6480
DOI: 10.1016/s1878-6480(15)30230-5
Popis: Background Endothelial cell (EC) dysfunction plays a central role in the pathogenesis of pulmonary arterial hypertension (PAH), promoting vasoconstriction, smooth muscle proliferation and inflammation. Objectives This study sought to test the hypothesis that nebivolol, a β 1 antagonist and β 2,3 -agonist, may improve PAH and reverse the PAH-related phenotype of pulmonary ECs (P-EC). Methods We compared the effects of nebivolol, with metoprolol, a first generation β 1 -selective β-blocker on human cultured PAH and control P-EC proliferation, vasoactive and proinflammatory factor production and crosstalk with PA smooth cells (PASMC). We assessed the effects of both β-blockers in precontracted PA rings. We also compared the effects of both β-blockers in experimentalPAH. Results PAH P-EC overexpressed the proinflammatory mediators IL-6 and MCP-1, the growth factor FGF2, 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. We confirmed that PAH P-EC proliferate 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 more potent than metoprolol in improving, cardiac function, pulmonary vascular remodeling and inflammation of rats with monocrotaline-induced pulmonary hypertension. 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.
Databáze: OpenAIRE
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