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(R) 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.
- Boehm, M.
- Arnold, N.
- Braithwaite, A.
- Pickworth, J.
- Lu, C.
- Novoyatleva, T.
- Kiely, D. G.
- Grimminger, F.
- Ghofrani, H. A.
- Weissmann, N.
- Seeger, W.
- Lawrie, A.
- Schermuly, R. T.
- Kojonazarov, B.
Keywords
- Eplerenone
- Pah
- Right ventricle
