Document Detail

Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1.
MedLine Citation:
PMID:  22140049     Owner:  NLM     Status:  MEDLINE    
Chronic hypertension induces cardiac remodeling, including left ventricular hypertrophy and fibrosis, through a combination of both hemodynamic and humoral factors. In previous studies, we showed that the heptapeptide ANG-(1-7) prevented mitogen-stimulated growth of cardiac myocytes in vitro, through a reduction in the activity of the MAPKs ERK1 and ERK2. In this study, saline- or ANG II-infused rats were treated with ANG-(1-7) to determine whether the heptapeptide reduces myocyte hypertrophy in vivo and to identify the signaling pathways involved in the process. ANG II infusion into normotensive rats elevated systolic blood pressure >50 mmHg, in association with increased myocyte cross-sectional area, ventricular atrial natriuretic peptide mRNA, and ventricular brain natriuretric peptide mRNA. Although infusion with ANG-(1-7) had no effect on the ANG II-stimulated elevation in blood pressure, the heptapeptide hormone significantly reduced the ANG II-mediated increase in myocyte cross-sectional area, interstitial fibrosis, and natriuretic peptide mRNAs. ANG II increased phospho-ERK1 and phospho-ERK2, whereas cotreatment with ANG-(1-7) reduced the phosphorylation of both MAPKs. Neither ANG II nor ANG-(1-7) altered the ERK1/2 MAPK kinase MEK1/2. However, ANG-(1-7) infusion, with or without ANG II, increased the MAPK phosphatase dual-specificity phosphatase (DUSP)-1; in contrast, treatment with ANG II had no effect on DUSP-1, suggesting that ANG-(1-7) upregulates DUSP-1 to reduce ANG II-stimulated ERK activation. These results indicate that ANG-(1-7) attenuates cardiac remodeling associated with a chronic elevation in blood pressure and upregulation of a MAPK phosphatase and may be cardioprotective in patients with hypertension.
Latronya T McCollum; Patricia E Gallagher; E Ann Tallant
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-02
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  302     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-01     Completed Date:  2012-03-20     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H801-10     Citation Subset:  IM    
The Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC 27157-1032, USA.
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MeSH Terms
Angiotensin I / pharmacology*
Angiotensin II / pharmacology*
Antihypertensive Agents / pharmacology
Cardiomegaly / drug therapy*,  metabolism,  pathology
Drug Interactions
Dual Specificity Phosphatase 1 / metabolism*
Fibrosis / metabolism,  pathology
Hypertension / physiopathology
MAP Kinase Signaling System / drug effects,  physiology
Myocardium / enzymology,  pathology
Peptide Fragments / pharmacology*
Rats, Sprague-Dawley
Up-Regulation / drug effects,  physiology
Vasoconstrictor Agents / pharmacology
Ventricular Remodeling / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Antihypertensive Agents; 0/Peptide Fragments; 0/Vasoconstrictor Agents; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 9041-90-1/Angiotensin I; EC Specificity Phosphatase 1

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