Abstract | BACKGROUND: METHODS: Cardiac pressure overload was produced by transverse aortic constriction (TAC). A total of 35 wide-type C57BL/6J mice were randomly divided into sham group, TAC group, TAC + olmesartan group, and TAC + olmsartan + DAPT group ( DAPT: γ- secretase inhibitor, Notch signaling inhibitor). Saline (10 mL·kg(-1)·d(-1)) or the same volume of olmesartan liquor (3 mg·kg(-1) d(-1)) was administered by gavage, and DAPT (10 μmole·kg(-1)·d(-1)) by peritoneal injection. After 28 days of treatment, cardiac hemodynamics, echocardiography, and histology were evaluated, followed by quantitative polymerase chain reaction of fetal gene ( ANP and SAA) expression. Notch1-related proteins and ERK1/2 were examined by western blot, and the serum level of angiotensin II was determined by means of enzyme-linked immunosorbent assay kits. RESULTS: CONCLUSIONS: Our findings identify a heretofore unknown pharmacological mechanism that olmesartan improves cardiac remodeling and function via DLL4/Notch1 pathway activation in mice with chronic pressure overload, which may present a new therapeutic target for hypertension.
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Authors | Jieyun You, Jian Wu, Guoliang Jiang, Jing Guo, Shijun Wang, Lei Li, Junbo Ge, Yunzeng Zou |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 61
Issue 2
Pg. 142-51
(Feb 2013)
ISSN: 1533-4023 [Electronic] United States |
PMID | 23188126
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Angiotensin II Type 1 Receptor Blockers
- Calcium-Binding Proteins
- DLL4 protein, mouse
- Dipeptides
- Imidazoles
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins
- N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
- Notch1 protein, mouse
- Receptor, Notch1
- Tetrazoles
- Angiotensin II
- olmesartan
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
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Topics |
- Adaptor Proteins, Signal Transducing
- Angiotensin II
(genetics)
- Angiotensin II Type 1 Receptor Blockers
(pharmacology)
- Animals
- Calcium-Binding Proteins
- Dipeptides
(pharmacology)
- Disease Models, Animal
- Fibrosis
- Hypertrophy, Left Ventricular
(drug therapy)
- Imidazoles
(pharmacology)
- Intracellular Signaling Peptides and Proteins
(metabolism)
- Male
- Membrane Proteins
(metabolism)
- Mice
- Mice, Inbred C57BL
- Microcirculation
(drug effects)
- Mitogen-Activated Protein Kinase 1
(genetics)
- Mitogen-Activated Protein Kinase 3
(genetics)
- Receptor, Notch1
(metabolism)
- Tetrazoles
(pharmacology)
- Up-Regulation
(drug effects)
- Ventricular Dysfunction, Left
(drug therapy)
- Ventricular Remodeling
(drug effects)
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