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Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension.


ABSTRACT: BACKGROUND:Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of aldosterone to the pathobiology of pulmonary arterial hypertension (PAH) and right ventricular (RV) heart failure is not fully understood. METHODS:The effects of Eplerenone (0.1% Inspra® mixed in chow) on pulmonary vascular and RV remodeling were evaluated in mice with pulmonary hypertension (PH) caused by Sugen5416 injection with concomitant chronic hypoxia (SuHx) and in a second animal model with established RV dysfunction independent from lung remodeling through surgical pulmonary artery banding. RESULTS:Preventive Eplerenone administration attenuated the development of PH and pathological remodeling of pulmonary arterioles. Therapeutic aldosterone antagonism - starting when RV dysfunction was established - normalized mineralocorticoid receptor gene expression in the right ventricle without direct effects on either RV structure (Cardiomyocyte hypertrophy, Fibrosis) or function (assessed by non-invasive echocardiography along with intra-cardiac pressure volume measurements), but significantly lowered systemic blood pressure. CONCLUSIONS:Our data indicate that aldosterone antagonism with Eplerenone attenuates pulmonary vascular rather than RV remodeling in PAH.

SUBMITTER: Boehm M 

PROVIDER: S-EPMC5833097 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension.

Boehm Mario M   Arnold Nadine N   Braithwaite Adam A   Pickworth Josephine J   Lu Changwu C   Novoyatleva Tatyana T   Kiely David G DG   Grimminger Friedrich F   Ghofrani Hossein A HA   Weissmann Norbert N   Seeger Werner W   Lawrie Allan A   Schermuly Ralph T RT   Kojonazarov Baktybek B  

BMC pulmonary medicine 20180302 1


<h4>Background</h4>Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of aldosterone to the pathobiology of pulmonary arterial hypertension (PAH) and right ventricular (RV) heart failure is not fully understood.<h4>Methods</h4>The effects of Eplerenone (0.1% Inspra® mixed in chow) on pulmonary vasc  ...[more]

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