Document Detail

Conservation of the cardiostimulant effects of (-)-norepinephrine across Ser49Gly and Gly389Arg beta(1)-adrenergic receptor polymorphisms in human right atrium in vitro.
MedLine Citation:
PMID:  12383575     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The goal of this study was to determine whether the cardiostimulant effects of the endogenous beta(1)-adrenergic receptor (AR) agonist, (-)-norepinephrine are modified by polymorphic (Serine49Glycine [Ser49Gly], Glycine389Arginine [Gly389Arg]) variants of beta(1)-ARs in the nonfailing adult human heart. BACKGROUND: Human heart beta(1)-ARs perform a crucial role in mediating the cardiostimulant effects of (-)-norepinephrine. An understanding of the significance of Ser49Gly and Gly389Arg polymorphisms in the human heart is beginning to emerge, but not as yet in adult patients who have coronary artery disease (CAD). METHODS: The potency and maximal effects of (-)-norepinephrine at beta(1)-ARs (in the presence of beta(2)-AR blockade with 50 nM ICI 118,551 [erythro-DL-1(7-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol]) for changes in contractile force and shortening of contractile cycle duration were determined in human right atrium in vitro from 87 patients undergoing coronary artery bypass grafting who were taking beta-blockers before surgery. A smaller sample of patients (n = 20) not taking beta-blockers was also investigated. Genotyping for two beta(1)-AR polymorphisms (Ser49Gly and Gly389Arg) was determined from a sample of blood taken at the time of surgery. RESULTS: (-)-Norepinephrine caused concentration-dependent increases in contractile force and reductions in time to reach peak force and time to reach 50% relaxation. There were no differences in the potency or maximal effects of (-)-norepinephrine in the right atrium from patients with different Ser49Gly and Gly389Arg polymorphisms. CONCLUSIONS: The cardiostimulant effects of (-)-norepinephrine at beta(1)-ARs were conserved across Ser49Gly and Gly389Arg polymorphisms in the right atrium of nonfailing hearts from patients with CAD managed with or without beta-blockers.
Peter Molenaar; Glenn Rabnott; Ian Yang; Kwun M Fong; Santiyagu M Savarimuthu; Li Li; Malcolm J West; Fraser D Russell
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  40     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-17     Completed Date:  2002-11-04     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1275-82     Citation Subset:  AIM; IM    
National Heart Foundation and Prince Charles Hospital Foundation Cardiovascular Research Centre, Department of Medicine, University of Queensland Chermside, Queensland, Australia.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology,  therapeutic use
Amino Acid Substitution / genetics*
Atrial Function*
Combined Modality Therapy
Coronary Artery Bypass
Coronary Disease / genetics*,  physiopathology*,  therapy
Dose-Response Relationship, Drug
Gene Frequency / genetics
Genetic Variation / genetics
Middle Aged
Myocardial Contraction / genetics,  physiology
Norepinephrine / administration & dosage,  physiology*
Polymorphism, Genetic / genetics*
Receptors, Adrenergic, beta-1 / agonists*
Sympathomimetics* / administration & dosage
Time Factors
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Receptors, Adrenergic, beta-1; 0/Sympathomimetics; 51-41-2/Norepinephrine

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