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The impact of phosphodiesterase-5 inhibition or angiotensin-converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload
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SYSNO ASEP 0582787 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The impact of phosphodiesterase-5 inhibition or angiotensin-converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload Author(s) Tykvartova, T. (CZ)
Miklovic, M. (CZ)
Kotrc, M. (CZ)
Škaroupková, P. (CZ)
Kazdová, L. (CZ)
Trnovská, J. (CZ)
Skop, V. (CZ)
Kolář, Michal (UMG-J) RID, ORCID
Novotný, Jiří (UMG-J) ORCID
Melenovský, V. (CZ)Number of authors 10 Article number e1172 Source Title PHARMACOL RES PERSPE - ISSN 2052-1707
Roč. 12, č. 1 (2024)Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords transgenic hypertensive-rats ; soluble epoxide hydrolase ; natriuretic-peptide ; myocardial-infarction ; renal dysfunction ; sildenafil ; expression ; pressure ; type-5 ; model ; heart failure ; phosphodiesterase-5 inhibition ; rats ; right ventricle ; volume overload OECD category Biochemistry and molecular biology Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 001150718200001 EID SCOPUS 85183654511 DOI 10.1002/prp2.1172 Annotation While phosphodiesterase-5 inhibition (PED5i) may prevent hypertrophy and failure in pressure-overloaded heart in an experimental model, the impact of PDE5i on volume-overload (VO)-induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long-term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto-caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin-converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure-volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6-fold, RV: 6.7-fold), and reduced load-independent systolic function (PRSW, LV:54%, RV:51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO-induced HF is not responsive to PDE5i therapy. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2025 Electronic address https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.1172
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