Document Detail


Inhibition of angiotensin-converting enzyme 2 exacerbates cardiac hypertrophy and fibrosis in Ren-2 hypertensive rats.
MedLine Citation:
PMID:  20300067     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Emerging evidence suggests that cardiac angiotensin-converting enzyme 2 (ACE2) may contribute to the regulation of heart function and hypertension-induced cardiac remodeling. We tested the hypothesis that inhibition of ACE2 in the hearts of (mRen2)27 hypertensive rats may accelerate progression of cardiac hypertrophy and fibrosis by preventing conversion of angiotensin II (Ang II) into the antifibrotic peptide, angiotensin-(1-7) (Ang-(1-7)).
METHODS: Fourteen male (mRen2)27 transgenic hypertensive rats (12 weeks old, 401 + or - 7 g) were administered either vehicle (0.9% saline) or the ACE2 inhibitor, MLN-4760 (30 mg/kg/day), subcutaneously via mini-osmotic pumps for 28 days.
RESULTS: Although ACE2 inhibition had no effect on average 24-h blood pressures, left ventricular (LV) Ang II content increased 24% in rats chronically treated with the ACE2 inhibitor (P < 0.05). Chronic ACE2 inhibition had no effect on plasma Ang II or Ang-(1-7) levels. Increased cardiac Ang II levels were associated with significant increases in both LV anterior, posterior, and relative wall thicknesses, as well as interstitial collagen fraction area and cardiomyocyte hypertrophy in the transgenic animals chronically treated with the ACE2 inhibitor. Cardiac remodeling was not accompanied by any further alterations in LV function.
CONCLUSIONS: These studies demonstrate that chronic inhibition of ACE2 causes an accumulation of cardiac Ang II, which exacerbates cardiac hypertrophy and fibrosis without having any further impact on blood pressure or cardiac function.
Authors:
Aaron J Trask; Leanne Groban; Brian M Westwood; Jasmina Varagic; Detlev Ganten; Patricia E Gallagher; Mark C Chappell; Carlos M Ferrario
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-18
Journal Detail:
Title:  American journal of hypertension     Volume:  23     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-18     Completed Date:  2010-08-20     Revised Date:  2013-08-23    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  687-93     Citation Subset:  IM    
Affiliation:
Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. aaron.trask@nationwidechildrens.org
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MeSH Terms
Descriptor/Qualifier:
Angiotensin I / blood
Angiotensin II / blood
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Blood Pressure / drug effects
Cardiomegaly / physiopathology*
Fibrosis / etiology,  pathology*
Heart Ventricles / drug effects,  enzymology
Imidazoles / pharmacology*
Leucine / analogs & derivatives*,  pharmacology
Male
Peptide Fragments / blood
Peptidyl-Dipeptidase A / drug effects*
Rats
Rats, Transgenic
Grant Support
ID/Acronym/Agency:
HL-51952/HL/NHLBI NIH HHS; HL-56973/HL/NHLBI NIH HHS; K08 AG026764/AG/NIA NIH HHS; K08 AG026764-05/AG/NIA NIH HHS; KO8-AG026764-04/AG/NIA NIH HHS; R01 AG033727/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
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/angiotensin I (1-7); 11128-99-7/Angiotensin II; 61-90-5/Leucine; 9041-90-1/Angiotensin I; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2
Comments/Corrections

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


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