Comparison of Macitentan and Bosentan on Right Ventricular Remodeling in a Rat Model of Non-vasoreactive Pulmonary Hypertension.
J Cardiovasc Pharmacol
; 66(5): 457-67, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26230396
ABSTRACT
AIMS:
We compared the efficacy of macitentan, a novel dual endothelin A/endothelin B receptor antagonist, with that of another dual endothelin receptor antagonist, bosentan, in a rat model of non-vasoreactive pulmonary hypertension (PH) with particular emphasis on right ventricular (RV) remodeling. METHODS ANDRESULTS:
Unlike monocrotaline or hypoxic/sugen rats, bleomycin-treated rats presented a non-vasoreactive PH characterized by the absence of pulmonary dilatation to adenosine. We therefore chose the bleomycin rat model to compare the effects of the maximally effective doses of macitentan and bosentan on pulmonary vascular and RV remodeling. Macitentan (100 mg·kg(-1)·d(-1)), but not bosentan (300 mg·kg(-1)·d(-1)), significantly prevented pulmonary vascular remodeling, RV hypertrophy, and cardiomyocyte diameter increase. Cardiac protection by macitentan was associated with a significant attenuation of genes related to cell hypertrophy and extracellular matrix remodeling. Microautoradiography and high performance liquid chromatography analysis showed greater distribution of macitentan than bosentan in the RV and pulmonary tissue.CONCLUSIONS:
Macitentan was more efficacious than bosentan in preventing the development of pulmonary and RV hypertrophies in a model of non-vasoreactive PH. Greater ability to distribute into the tissue could contribute to the greater structural improvement by macitentan compared with bosentan.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Sulfonamidas
/
Função Ventricular Direita
/
Hipertrofia Ventricular Direita
/
Remodelação Ventricular
/
Antagonistas dos Receptores de Endotelina
/
Ventrículos do Coração
/
Hipertensão Pulmonar
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido