Document Detail

Upregulation of beta-adrenergic receptors in heart failure due to volume overload.
MedLine Citation:
PMID:  15734891     Owner:  NLM     Status:  MEDLINE    
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 or losartan (20 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.
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    
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Winnipeg, MB R2H 2A6, Canada.
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MeSH Terms
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
Isoproterenol / pharmacology
Myocardium / metabolism
Protein-Serine-Threonine Kinases / metabolism
Receptors, Adrenergic, beta / metabolism*
Subcellular Fractions / metabolism
Tissue Distribution
beta-Adrenergic Receptor Kinases
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 Kinases; EC AMP-Dependent Protein Kinases; EC Receptor Kinases; EC Receptor Kinase 5; EC protein, rat

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

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