Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure.
Aminobutyrates
/ administration & dosage
Angiotensin Receptor Antagonists
/ administration & dosage
Animals
Biphenyl Compounds
Drug Combinations
Heart
/ diagnostic imaging
Heart Failure
/ drug therapy
Male
Myocardial Reperfusion Injury
/ drug therapy
Myocardium
/ metabolism
Neovascularization, Physiologic
Neprilysin
/ antagonists & inhibitors
Organotechnetium Compounds
/ pharmacokinetics
Peptides, Cyclic
/ pharmacokinetics
Rats
Rats, Inbred Lew
Single Photon Emission Computed Tomography Computed Tomography
Tetrazoles
/ administration & dosage
Valsartan
/ administration & dosage
Vascular Endothelial Growth Factor A
/ genetics
Ventricular Remodeling
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 04 2019
08 04 2019
Historique:
received:
27
11
2018
accepted:
19
03
2019
entrez:
10
4
2019
pubmed:
10
4
2019
medline:
7
10
2020
Statut:
epublish
Résumé
Angiotensin receptor blocker-neprilysin inhibitor (ARNi) therapy improves the prognosis of heart failure patients. However, the mechanisms remain unclear. This study investigated the biological effects of ARNi with neprilysin inhibitor sacubitril and angiotensin receptor blocker valsartan on myocardial remodeling and cardiac perfusion in experimental heart failure (HF) after myocardial infarction (MI). Male Lewis rats (10-weeks old) with confirmed HF were randomized one-week post-MI to treatment with vehicle (water), sacubitril/valsartan or valsartan, as comparator group, for either 1 or 5 weeks. Sacubitril/valsartan for 1-week limited LV contractile dysfunction vs. vehicle and both sacubitril/valsartan and valsartan attenuated progressive LV dilation after 1 and 5 weeks treatment. After 5 weeks, both sacubitril/valsartan and valsartan reduced CTGF expression in the remote myocardium, although only sacubitril/valsartan prevented interstitial fibrosis. In the border zone, sacubitril/valsartan and valsartan reduced hypertrophic markers, but only sacubitril/valsartan reduced cardiomyocyte size and increased VEGFA expression. In the infarct, sacubitril/valsartan induced an early uptake of
Identifiants
pubmed: 30962467
doi: 10.1038/s41598-019-42113-0
pii: 10.1038/s41598-019-42113-0
pmc: PMC6453892
doi:
Substances chimiques
Aminobutyrates
0
Angiotensin Receptor Antagonists
0
Biphenyl Compounds
0
Drug Combinations
0
Organotechnetium Compounds
0
Peptides, Cyclic
0
Tetrazoles
0
Vascular Endothelial Growth Factor A
0
Valsartan
80M03YXJ7I
Neprilysin
EC 3.4.24.11
technetium 99m NC 100692
H0X34CV8RR
sacubitril and valsartan sodium hydrate drug combination
WB8FT61183
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5791Subventions
Organisme : NCRR NIH HHS
ID : S10 RR023602
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIH HHS
ID : S10 OD021845
Pays : United States
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