Document Detail

Beta-adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic G(salpha) mouse.
MedLine Citation:
PMID:  10487769     Owner:  NLM     Status:  MEDLINE    
Transgenic (TG) mice with cardiac G(salpha) overexpression exhibit enhanced inotropic and chronotropic responses to sympathetic stimulation, but develop cardiomyopathy with age. We tested the hypothesis that cardiomyopathy in TG mice with G(salpha) overexpression could be averted with chronic beta-adrenergic receptor (beta-AR) blockade. TG mice and age-matched wild-type littermates were treated with the beta-AR blocker propranolol for 6-7 months, starting at a time when the cardiomyopathy was developing but was not yet severe enough to induce significant cardiac depression (9.5 months of age), and ending at a time when cardiac depression and cardiomyopathy would have been clearly manifest (16 months of age). Propranolol treatment, which can induce cardiac depression in the normal heart, actually prevented cardiac dilation and the depressed left ventricular function characteristic of older TG mice, and abolished premature mortality. Propranolol also prevented the increase in myocyte cross-sectional area and myocardial fibrosis. Myocyte apoptosis, already apparent in 9-month-old TG mice, was actually eliminated by chronic propranolol. This study indicates that chronic sympathetic stimulation over an extended period is deleterious and results in cardiomyopathy. Conversely, beta-AR blockade is salutary in this situation and can prevent the development of cardiomyopathy.
K Asai; G P Yang; Y J Geng; G Takagi; S Bishop; Y Ishikawa; R P Shannon; T E Wagner; D E Vatner; C J Homcy; S F Vatner
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  104     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-04     Completed Date:  1999-10-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  551-8     Citation Subset:  AIM; IM; S    
Weis Center for Research, Penn State College of Medicine, Danville, Pennsylvania 17822, USA.
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MeSH Terms
Adenylate Cyclase / metabolism
Adrenergic beta-Antagonists / therapeutic use*
Blood Pressure
Cardiomyopathy, Dilated / genetics,  pathology,  prevention & control*,  ultrasonography
Cyclic AMP / biosynthesis
Endomyocardial Fibrosis / genetics,  pathology,  prevention & control*,  ultrasonography
Enzyme Activation
GTP-Binding Protein alpha Subunits, Gs / biosynthesis*,  genetics
Gene Expression Regulation
Heart Rate
Mice, Transgenic
Myocardium / pathology
Myosin Heavy Chains / genetics
Promoter Regions, Genetic
Propranolol / therapeutic use*
Receptors, Adrenergic, beta / drug effects,  physiology*
Recombinant Fusion Proteins / biosynthesis,  genetics
Signal Transduction / drug effects*,  genetics
Ventricular Dysfunction, Left / genetics,  pathology,  prevention & control*,  ultrasonography
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Myosin Heavy Chains; 0/Receptors, Adrenergic, beta; 0/Recombinant Fusion Proteins; 525-66-6/Propranolol; 60-92-4/Cyclic AMP; EC Protein alpha Subunits, Gs; EC Cyclase

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

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