| Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts. | |
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MedLine Citation:
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PMID: 20071356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Our aim was to determine the contribution of the three angiotensin (Ang) II receptor subtypes (AT(1a), AT(1b), AT(2)) to coronary responsiveness, cardiac histopathology, and tissue Ang II levels using mice deficient for one, two, or all three Ang II receptors. METHODS AND RESULTS: Hearts of knockout mice and their wild-type controls were collected for histochemistry or perfused according to Langendorff, and kidneys were removed to measure tissue Ang II. Ang II dose-dependently decreased coronary flow (CF) and left ventricular systolic pressure (LVSP), and these effects were absent in all genotypes deficient for AT(1a), independently of AT(1b) and AT(2). The deletion of Ang II receptors had an effect neither on the morphology of medium-sized vessels in the heart nor on the development of fibrosis. However, the lack of both AT(1) subtypes was associated with atrophic changes in the myocardium, a reduced CF and a reduced LVSP. AT(1a) deletion alone, independently of the presence or absence of AT(1b) and/or AT(2), reduced renal Ang II by 50% despite a five-fold rise of plasma Ang II. AT(1b) deletion, on top of AT(1a) deletion (but not alone), further decreased tissue Ang II, while increasing plasma Ang II. In mice deficient for all three Ang II receptors, renal Ang II was located only extracellularly. CONCLUSION: The lack of both AT(1) subtypes led to a baseline reduction of CF and LVSP, and the effects of Ang II on CF and LVSP were found to be exclusively mediated via AT(1a). The lack of AT(1a) or AT(1b) does not influence the development or maintenance of normal cardiac morphology, whereas deficiency for both receptors led to atrophic changes in the heart. Renal Ang II levels largely depend on AT(1) binding of extracellularly generated Ang II, and in the absence of all three Ang II receptors, renal Ang II is only located extracellularly. |
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Authors:
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Joep H M van Esch; Florian Gembardt; Anja Sterner-Kock; Silvia Heringer-Walther; Thu H Le; Dirk Lassner; Theo Stijnen; Thomas M Coffman; Heinz-Peter Schultheiss; A H Jan Danser; Thomas Walther |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-12 |
Journal Detail:
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Title: Cardiovascular research Volume: 86 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-13 Completed Date: 2010-06-03 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 401-9 Citation Subset: IM |
Affiliation:
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Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
/
administration & dosage,
blood,
metabolism* Animals Atrophy Coronary Circulation Fibrosis Genotype Kidney / metabolism Male Mice Mice, Knockout Myocardium / metabolism*, pathology Natriuretic Peptide, Brain / metabolism Perfusion Phenotype Receptor, Angiotensin, Type 1 / deficiency*, genetics Receptor, Angiotensin, Type 2 / deficiency*, genetics Ventricular Function, Left Ventricular Pressure Ventricular Remodeling |
| Grant Support | |
ID/Acronym/Agency:
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5R01HL082722-02/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Agtr1a protein, mouse; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 11128-99-7/Angiotensin II; 114471-18-0/Natriuretic Peptide, Brain |
| Comments/Corrections | |
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