Document Detail

Angiotensin(1-7) blunts hypertensive cardiac remodeling by a direct effect on the heart.
MedLine Citation:
PMID:  18845809     Owner:  NLM     Status:  MEDLINE    
Angiotensin-converting enzyme 2 (ACE2) converts the vasopressor angiotensin II (Ang II) into angiotensin (1-7) [Ang(1-7)], a peptide reported to have vasodilatory and cardioprotective properties. Inactivation of the ACE2 gene in mice has been reported by one group to result in an accumulation of Ang II in the heart and an age-related defect in cardiac contractility. A second study confirmed the role of ACE2 as an Ang II clearance enzyme but failed to reproduce the contractility defects previously reported in ACE2-deficient mice. The reasons for these differences are unclear but could include differences in the accumulation of Ang II or the deficiencies in Ang(1-7) in the mouse models used. As a result, the roles of ACE2, Ang II, and Ang(1-7) in the heart remain controversial. Using a novel strategy, we targeted the chronic overproduction of either Ang II or Ang(1-7) in the heart of transgenic mice and tested their effect on age-related contractility and on cardiac remodeling in response to a hypertensive challenge. We demonstrate that a chronic accumulation of Ang II in the heart does not result in cardiac contractility defects, even in older (8-month-old) mice. Likewise, transgenic animals with an 8-fold increase in Ang(1-7) peptide in the heart exhibited no differences in resting blood pressure or cardiac contractility as compared to age-matched controls, but they had significantly less ventricular hypertrophy and fibrosis than their nontransgenic littermates in response to a hypertensive challenge. Analysis of downstream signaling cascades demonstrates that cardiac Ang(1-7) selectively modulates some of the downstream signaling effectors of cardiac remodeling. These results suggest that Ang(1-7) can reduce hypertension-induced cardiac remodeling through a direct effect on the heart and raise the possibility that pathologies associated with ACE2 inactivation are mediated in part by a decrease in production of Ang(1-7).
Chantal Mercure; Alvaro Yogi; Glaucia E Callera; Anna B Aranha; Michael Bader; Anderson J Ferreira; Robson A S Santos; Thomas Walther; Rhian M Touyz; Timothy L Reudelhuber
Related Documents :
8583479 - Discovery of losartan, the first angiotensin ii receptor antagonist.
10715269 - Losartan and its metabolite e3174 modify cardiac delayed rectifier k(+) currents.
18161009 - Increased pressure stimulates aberrant dendritic cell maturation.
3820939 - The effects of angiotensin ii and norepinephrine on afferent arterioles in the rat.
23743499 - A prospective evaluation of hemodynamic management in acute spinal cord injury patients.
10899299 - Role of brain angiotensin ii in renal nerve inhibition elicited by volume expansion in ...
22920049 - How do compliance, convenience, and tolerability affect blood pressure goal rates?
1877349 - Oedema-preventing mechanisms in a low-compliant tissue: studies on the rat tail.
10713029 - Effect of pericardial pressure on human coronary circulation.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-09
Journal Detail:
Title:  Circulation research     Volume:  103     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-25     Completed Date:  2008-12-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1319-26     Citation Subset:  IM    
Clinical Research Institute of Montreal (IRCM), Montreal, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Angiotensin I / pharmacology*
Angiotensin II / genetics
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Antihypertensive Agents / pharmacology*
Blood Pressure / drug effects
Cardiomegaly / enzymology,  genetics
Crosses, Genetic
Heart / anatomy & histology,  drug effects,  physiology,  physiopathology
Hypertension / prevention & control*
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Myocardium / metabolism,  pathology
Peptide Fragments / pharmacology*
Peptidyl-Dipeptidase A / pharmacology
Renin-Angiotensin System / drug effects
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Peptide Fragments; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 9041-90-1/Angiotensin I; EC A; EC 3.4.17.-/angiotensin converting enzyme 2
Comment In:
Circ Res. 2008 Nov 21;103(11):1197-9   [PMID:  19028917 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Characterization of acute brain injuries and neurobehavioral profiles in a rabbit model of germinal ...
Next Document:  Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional contro...