|Beta-adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic G(salpha) mouse.|
|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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|Type: Journal Article|
|Title: The Journal of clinical investigation Volume: 104 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 1999 Sep|
|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|
|Languages: eng Pagination: 551-8 Citation Subset: AIM; IM; S|
|Weis Center for Research, Penn State College of Medicine, Danville, Pennsylvania 17822, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Adrenergic beta-Antagonists / therapeutic use*
Cardiomyopathy, Dilated / genetics, pathology, prevention & control*, ultrasonography
Cyclic AMP / biosynthesis
Endomyocardial Fibrosis / genetics, pathology, prevention & control*, ultrasonography
GTP-Binding Protein alpha Subunits, Gs / biosynthesis*, genetics
Gene Expression Regulation
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
|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 126.96.36.199/GTP-Binding Protein alpha Subunits, Gs; EC 188.8.131.52/Adenylate Cyclase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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