Document Detail


Progressive cardiac hypertrophy and dysfunction in atrial natriuretic peptide receptor (GC-A) deficient mice.
MedLine Citation:
PMID:  11907014     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate how permanent inhibition of guanylyl cyclase A receptor (GC-A) affects cardiac function.
METHODS: Hearts of GC-A-/- and corresponding wild type mice (GC-A+/+) were characterised by histological, western blotting, and northern blotting analyses. Cardiac function was evaluated in isolated, working heart preparations.
RESULTS: At 4 months of age, GC-A-/- mice had global cardiac hypertrophy (about a 40% increase in cardiac weight) without interstitial fibrosis. Examination of heart function found a significant delay in the time of relaxation; all other parameters of cardiac contractility were similar to those in wild type mice. At 12 months, the hypertrophic changes were much more severe (about a 61% increase in cardiac weight), together with a shift in cardiac gene expression (enhanced concentrations of atrial natriuretic peptide (3.8-fold), B type natriuretic peptide (2-fold), beta myosin heavy chain (1.6-fold) and alpha skeletal actin (1.7-fold) mRNA), increased expression of cytoskeletal tubulin and desmin (by 29.6% and 25.6%, respectively), and pronounced interstitial fibrosis. These changes were associated with significantly impaired cardiac contractility (+dP/dt decreased by about 10%) and relaxation (-dP/dt decreased by 21%), as well as depressed contractile responses to pressure load (all p < 0.05).
CONCLUSIONS: Chronic hypertension in GC-A-/- mice is associated with progressive cardiac changes--namely, initially compensated cardiomyocyte hypertrophy, which is complicated by interstitial fibrosis and impaired cardiac contractility at later stages.
Authors:
M Kuhn; R Holtwick; H A Baba; J C Perriard; W Schmitz; E Ehler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Heart (British Cardiac Society)     Volume:  87     ISSN:  1468-201X     ISO Abbreviation:  Heart     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-21     Completed Date:  2002-04-16     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  9602087     Medline TA:  Heart     Country:  England    
Other Details:
Languages:  eng     Pagination:  368-74     Citation Subset:  AIM; IM    
Affiliation:
Institute of Pharmacology and Toxicology, Westfälische Wilhelms-Universität Münster, Münster, Germany. mkuhn@uni-muenster.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology
Blotting, Northern
Blotting, Western
Cardiomegaly / etiology*,  pathology,  physiopathology
Endomyocardial Fibrosis / etiology
Guanylate Cyclase*
Hypertension / etiology
Immunohistochemistry
Male
Mice
Receptors, Atrial Natriuretic Factor*
Receptors, Cell Surface / deficiency*
Ventricular Function, Left / physiology
Chemical
Reg. No./Substance:
0/Receptors, Cell Surface; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/Receptors, Atrial Natriuretic Factor; EC 4.6.1.2/atrial natriuretic factor receptor A
Comments/Corrections
Comment In:
Heart. 2002 Apr;87(4):314-5   [PMID:  11906995 ]

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