| Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1-7) in transgenic Ren-2 hypertensive rats. | |
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MedLine Citation:
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PMID: 17308000 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiotensin-converting enzyme-2 (ACE2) converts angiotensin II (ANG II) to angiotensin-(1-7) [ANG-(1-7)], and this enzyme may serve as a key regulatory juncture in various tissues. Although the heart expresses ACE2, the extent that the enzyme participates in the cardiac processing of ANG II and ANG-(1-7) is equivocal. Therefore, we utilized the Langendorff preparation to characterize the ACE2 pathway in isolated hearts from male normotensive Sprague-Dawley [Tg((-))] and hypertensive [mRen2]27 [Tg((+))] rats. During a 60-min recirculation period with 10 nM ANG II, the presence of ANG-(1-7) was assessed in the cardiac effluent. ANG-(1-7) generation from ANG II was similar in both the normal and hypertensive hearts [Tg((-)): 510 +/- 55 pM, n=20 vs. Tg((+)): 497 +/- 63 pM, n=14] with peak levels occurring at 30 min after administration of the peptide. ACE2 inhibition (MLN-4760, 1 microM) significantly reduced ANG-(1-7) production by 83% (57 +/- 19 pM, P<0.01, n=7) in the Tg((+)) rats, whereas the inhibitor had no significant effect in the Tg((-)) rats (285 +/- 53 pM, P>0.05, n=10). ACE2 activity was found in the effluent of perfused Tg((-)) and Tg((+)) hearts, and it was highly associated with ACE2 protein expression (r=0.78). This study is the first demonstration for a direct role of ACE2 in the metabolism of cardiac ANG II in the hypertrophic heart of hypertensive rats. We conclude that predominant expression of cardiac ACE2 activity in the Tg((+)) may be a compensatory response to the extensive cardiac remodeling in this strain. |
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Authors:
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Aaron J Trask; David B Averill; Detlev Ganten; Mark C Chappell; Carlos M Ferrario |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-02-16 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 292 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-06-12 Completed Date: 2007-08-02 Revised Date: 2012-07-03 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H3019-24 Citation Subset: IM |
Affiliation:
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Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. atrask@wfubmc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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metabolism* Angiotensin-Converting Enzyme Inhibitors / pharmacology Animals Animals, Genetically Modified Cardiomegaly / enzymology, genetics, metabolism*, pathology Disease Models, Animal Half-Life Hypertension / complications, enzymology, genetics, metabolism*, pathology Imidazoles / pharmacology Kinetics Leucine / analogs & derivatives, pharmacology Male Mice Myocardium / enzymology, metabolism*, pathology Peptide Fragments / metabolism* Peptidyl-Dipeptidase A / metabolism* Rats Rats, Sprague-Dawley / genetics Renin / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL51952/HL/NHLBI NIH HHS; HL56973/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-(1-carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)ethylamino)-4-methylpentanoic acid; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Imidazoles; 0/Peptide Fragments; 0/Ren2 protein, mouse; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 61-90-5/Leucine; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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