Effects of combined angiotensin II receptor antagonism and neprilysin inhibition in experimental pulmonary hypertension and right ventricular failure.

Autor: Andersen S; Department of Cardiology, Aarhus University Hospital, Denmark. Electronic address: stineandersen@clin.au.dk., Axelsen JB; Department of Cardiology, Aarhus University Hospital, Denmark., Ringgaard S; MR Centre, Aarhus University Hospital, Denmark., Nyengaard JR; Core Center for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Denmark., Hyldebrandt JA; Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Denmark., Bogaard HJ; Department of Pulmonology, Amsterdam UMC, the Netherlands., de Man FS; Department of Pulmonology, Amsterdam UMC, the Netherlands., Nielsen-Kudsk JE; Department of Cardiology, Aarhus University Hospital, Denmark., Andersen A; Department of Cardiology, Aarhus University Hospital, Denmark.
Jazyk: angličtina
Zdroj: International journal of cardiology [Int J Cardiol] 2019 Oct 15; Vol. 293, pp. 203-210. Date of Electronic Publication: 2019 Jun 29.
DOI: 10.1016/j.ijcard.2019.06.065
Abstrakt: Background: Combined angiotensin II receptor antagonism and neprilysin inhibition by LCZ696 reduces morbidity and mortality in heart failure patients and works by reducing RAAS activity and increasing cGMP levels. This study aims to evaluate the effects of LCZ696 in rats with pulmonary hypertension and right ventricular (RV) failure.
Methods: Pulmonary hypertension was induced in rats (n = 34) by combined exposure to the vascular endothelial growth factor-receptor antagonist SU5416 and hypoxia (SuHx). To distinguish pulmonary vascular from cardiac effects, isolated RV failure was induced by pulmonary trunk banding (PTB) in another group of rats (n = 40). In both models, the development of RV dysfunction was verified before randomization to treatment with LCZ696 (60 mg/kg/day) or vehicle for five weeks.
Results: In the SuHx rats, LCZ696 treatment reduced the increase in RV pressure and the development of RV hypertrophy and RV dilatation compared with vehicle treatment. LCZ696 also reduced wall thickness of the smaller pulmonary arteries. In the PTB rats, LCZ696 treatment did not have any effects on RV hypertrophy or function.
Conclusions: Combined angiotensin II receptor antagonism and neprilysin inhibition reduced RV systolic pressure, hypertrophy, and dilatation in rats with pulmonary hypertension. These effects seem secondary to pulmonary vascular changes, including reduced pulmonary vascular remodeling, as similar effects were not seen in rats with isolated RV failure. LCZ696 may have a therapeutic potential in the treatment of pulmonary hypertension.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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