Document Detail


Effects of adrenomedullin on human myocyte contractile function and beta-adrenergic response.
MedLine Citation:
PMID:  12490969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Adrenomedullin has been demonstrated to cause systemic vasodilation, and increased plasma adrenomedullin levels have been observed in cardiovascular disease states such as heart failure. While adrenomedullin receptors have been localized to the myocardium, the effects of adrenomedullin on human myocyte contractility remained unknown. METHODS AND RESULTS: Left ventricular myocytes were isolated from myocardial biopsies of patients (n = 16) undergoing elective coronary artery bypass surgery with normal left ventricular ejection fractions (51 +/- 1%). A total of 233 left ventricular myocytes were studied by videomicroscopy. Myocyte shortening velocity (microm/s) was measured at baseline and following the addition of either 3 nM, 30 nM, or 60 nM of adrenomedullin. The change in myocyte shortening velocity with increasing concentrations of adrenomedullin was computed. At all concentrations, adrenomedullin reduced myocyte shortening velocity from baseline values (P < 0.05). Next, the potential interaction of adrenomedullin with the beta-adrenergic receptor system was examined using 25 nM isoproterenol. The beta-adrenergic receptor-mediated increase in the myocyte shortening velocity was blunted with adrenomedullin (29 +/- 7 vs 63 +/- 13 microm/s, P < 0.05). CONCLUSIONS: These unique findings demonstrate that adrenomedullin reduced contractility in isolated human left ventricular myocytes and exhibited a negative interaction with the beta-adrenergic receptor system. Past studies have shown that adrenomedullin induces nitric oxide synthesis and that nitric oxide can uncouple myocyte metabolism. Thus, while adrenomedullin causes systemic vasodilation, this peptide can also exert a negative contractile effect in human left ventricular myocytes.
Authors:
Rupak Mukherjee; M Marlina Multani; Jeffrey A Sample; Kathryn B Dowdy; James L Zellner; Donald B Hoover; Francis G Spinale
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology and therapeutics     Volume:  7     ISSN:  1074-2484     ISO Abbreviation:  J. Cardiovasc. Pharmacol. Ther.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-12-19     Completed Date:  2003-06-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9602617     Medline TA:  J Cardiovasc Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-40     Citation Subset:  IM    
Affiliation:
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenomedullin
Aged
Analysis of Variance
Depression, Chemical
Humans
Middle Aged
Myocardial Contraction / drug effects*,  physiology
Myocytes, Cardiac / drug effects*,  physiology
Peptides / pharmacology*
Receptors, Adrenergic, beta / physiology*
Grant Support
ID/Acronym/Agency:
HL-45024/HL/NHLBI NIH HHS; HL-97012/HL/NHLBI NIH HHS; P01-48788//PHS HHS
Chemical
Reg. No./Substance:
0/Peptides; 0/Receptors, Adrenergic, beta; 148498-78-6/Adrenomedullin

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


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