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.

• Authors: Mario Boehm, Nadine Arnold, Adam Braithwaite, Josephine Pickworth, Changwu Lu, Tatyana Novoyatleva, David G Kiely, Friedrich Grimminger, Hossein A Ghofrani, Norbert Weissmann, Werner Seeger, Allan Lawrie, Ralph T Schermuly, Baktybek Kojonazarov
• Journal: BMC pulmonary medicine (BMC Pulm Med) Vol. 18 Issue 1 Pg. 41 (Mar 02 2018) ISSN: 1471-2466 [Electronic] England
• PMID: 29499691 (Publication Type: Journal Article)

Chemical References

• Mineralocorticoid Receptor Antagonists
• Eplerenone

Topics

• Animals
• Arterial Pressure (drug effects)
• Disease Models, Animal
• Eplerenone (pharmacology)
• Heart Ventricles (pathology)
• Hypertension, Pulmonary (drug therapy, physiopathology)
• Hypoxia (physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mineralocorticoid Receptor Antagonists (pharmacology)
• Pulmonary Artery (physiopathology)
• Ventricular Dysfunction, Right (drug therapy, physiopathology)
• Ventricular Remodeling (drug effects)