Document Detail


Protecting the myocardium: a role for the beta2 adrenergic receptor in the heart.
MedLine Citation:
PMID:  15071399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The sympathetic nervous system enhances cardiac muscle function by activating beta adrenergic receptors (betaARs). Recent studies suggest that chronic betaAR stimulation is detrimental, however, and that it may play a role in the clinical deterioration of patients with congestive heart failure. To examine the impact of chronic beta1AR and beta2AR subtype stimulation individually, we studied the cardiovascular effects of catecholamine infusions in betaAR subtype knockout mice (beta1KO, beta2KO). DESIGN: Prospective, randomized, experimental study. SETTING: Animal research laboratory. SUBJECTS: beta1KO and beta2KO mice and wild-type controls. INTERVENTIONS: The animals were subjected to 2 wks of continuous infusion of the betaAR agonist isoproterenol. Analyses of cardiac function and structure were performed during and 3 days after completion of the infusions. Functional studies included graded exercise treadmill testing, in vivo assessments of left ventricular function using Mikro-Tip catheter transducers, right ventricular pressure measurements, and analyses of organ weight to body weight ratios. Structural studies included heart weight measurements, assessments of myocyte ultrastructure using electron microscopy, and in situ terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling staining to quantitate myocyte apoptosis. MEASUREMENTS AND MAIN RESULTS: We found that isoproterenol-treated beta2KO mice experienced greater mortality rates (p =.001, chi-square test using Fisher's exact method) and increased myocyte apoptosis at 3- and 7-day time points (p =.04 and p =.0007, respectively, two-way analysis of variance). CONCLUSION: The results of this study suggest that in vivo beta2AR activation is antiapoptotic and contributes to myocardial protection.
Authors:
Andrew J Patterson; Weizhong Zhu; Amy Chow; Rani Agrawal; Jon Kosek; Rui Ping Xiao; Brian Kobilka
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Critical care medicine     Volume:  32     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-08     Completed Date:  2004-05-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1041-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesia, Stanford University, Stanford, CA, USA. ajplanes@leland.stanford.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology*
Animals
Apoptosis / drug effects*
Exercise Test / drug effects
Heart / innervation
Infusions, Intravenous
Isoproterenol / pharmacology*
Male
Mice
Mice, Knockout
Microscopy, Electron
Myocardial Contraction / drug effects*
Myocardium / pathology*
Receptors, Adrenergic, beta-1 / drug effects,  genetics
Receptors, Adrenergic, beta-2 / drug effects*,  genetics
Survival Rate
Sympathetic Nervous System / drug effects
Ventricular Function, Left / drug effects*
Ventricular Function, Right / drug effects*
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 7683-59-2/Isoproterenol

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


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