| Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation. | |
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MedLine Citation:
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PMID: 17557919 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac beta-adrenergic receptor (beta-AR) signaling and left ventricular (LV) responses to beta-AR stimulation are impaired with aging. It is shown that exercise and beta-AR blockade have a favorable effect on cardiac and vascular beta-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on beta-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg.kg(-1).day(-1) for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to beta-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac beta-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of beta-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the aged heart, leading to improved beta-AR responsiveness and corresponding LV inotropic reserve. |
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Authors:
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Dario Leosco; Giuseppe Rengo; Guido Iaccarino; Amelia Filippelli; Anastasios Lymperopoulos; Carmela Zincarelli; Francesca Fortunato; Luca Golino; Massimo Marchese; Giovanni Esposito; Antonio Rapacciuolo; Barbara Rinaldi; Nicola Ferrara; Walter J Koch; Franco Rengo |
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Publication Detail:
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Type: Journal Article Date: 2007-06-08 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 293 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-09-06 Completed Date: 2007-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1596-603 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Cardiovascular Sciences and Immunology, University Federico II, Via Pansini 5, Edificio 2, 80131 Naples, Italy. dleosco@unina.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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metabolism Adrenergic beta-Agonists / pharmacology Adrenergic beta-Antagonists / pharmacology* Aging / physiology* Animals Blood Pressure / physiology Heart / drug effects, physiology* Heart Rate / physiology Isoproterenol / pharmacology Male Metoprolol / pharmacology Myocardial Contraction / physiology Physical Conditioning, Animal / physiology* Random Allocation Rats Rats, Inbred WKY Receptors, Adrenergic, beta / drug effects, physiology* Signal Transduction / physiology* Ventricular Function, Left / physiology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Adrenergic beta-Antagonists; 0/Receptors, Adrenergic, beta; 37350-58-6/Metoprolol; 7683-59-2/Isoproterenol; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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