Document Detail


Upregulation of beta-adrenergic receptors in heart failure due to volume overload.
MedLine Citation:
PMID:  15734891     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To examine the mechanisms of changes in beta-adrenergic signal transduction in heart failing due to volume overload, we studied the status of beta-adrenoceptors (beta-ARs), G protein-coupled receptor kinase (GRK), and beta-arrestin in heart failure due to aortocaval shunt (AVS). Heart failure in rats was induced by creating AVS for 16 wk, and beta-AR binding, GRK activity, as well as their protein content, and mRNA levels were determined in both left and right ventricles. The density and protein content for beta1-ARs, unlike those for beta2-ARs, were increased in the failing hearts. Furthermore, protein contents for GRK isoforms and beta-arrestin-1 were decreased in membranous fractions and increased in cytosolic fractions from the failing hearts. On the other hand, steady-state mRNA levels for beta1-ARs and GRK2, as well as protein content for Gbetagamma-subunits, did not change in the failing heart. Basal cardiac function was depressed; however, both in vivo and ex vivo positive inotropic responses of the failing hearts to isoproterenol were augmented. Treatment of AVS animals with imidapril (1 mg.kg(-1).day(-1)) or losartan (20 mg.kg(-1).day(-1)) retarded the progression of heart failure; partially prevented changes in beta1-ARs, GRKs, and beta-arrestin-1 in the failing myocardium; and attenuated the increase in positive inotropic effect of isoproterenol. These results indicate that upregulation of beta1-ARs is associated with subcellular redistribution of GRKs and beta-arrestin-1 in the failing heart due to volume overload. Furthermore, attenuation of alterations in beta-adrenergic system by imidapril or losartan may be due to blockade of the renin-angiotensin system in the AVS model of heart failure.
Authors:
Xi Wang; Emmanuelle Sentex; Harjot K Saini; Donald Chapman; Naranjan S Dhalla
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-02-25
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  289     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-17     Completed Date:  2005-08-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H151-9     Citation Subset:  IM    
Affiliation:
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Winnipeg, MB R2H 2A6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrestins / metabolism
Blood Volume*
Cardiotonic Agents / pharmacology
Cyclic AMP-Dependent Protein Kinases / metabolism
G-Protein-Coupled Receptor Kinase 5
GTP-Binding Protein beta Subunits / metabolism
GTP-Binding Protein gamma Subunits / metabolism
Heart Failure / etiology*,  metabolism*,  physiopathology
Hemodynamics
Isoproterenol / pharmacology
Myocardium / metabolism
Protein-Serine-Threonine Kinases / metabolism
Rats
Receptors, Adrenergic, beta / metabolism*
Subcellular Fractions / metabolism
Tissue Distribution
Up-Regulation*
beta-Adrenergic Receptor Kinases
Chemical
Reg. No./Substance:
0/Arrestins; 0/Cardiotonic Agents; 0/GTP-Binding Protein beta Subunits; 0/GTP-Binding Protein gamma Subunits; 0/Receptors, Adrenergic, beta; 0/beta-arrestin; 7683-59-2/Isoproterenol; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.15/beta-Adrenergic Receptor Kinases; EC 2.7.11.16/G-Protein-Coupled Receptor Kinase 5; EC 2.7.11.16/Gprk5 protein, rat

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


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