Document Detail


Combined effects of metoprolol and spironolactone in dilated cardiomyopathic hamsters.
MedLine Citation:
PMID:  12352316     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The use of beta-blockers reduces angiotensin II levels, but could not adequately suppress aldosterone production. Thus, the combination of a beta-blocker with an aldosterone receptor antagonist could exert additive effects. The effects of metoprolol and spironolactone and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters (CMH) were investigated. The Bio TO-2 dilated strain of CMH was treated orally with metoprolol (10 mg/kg/day), spironolactone (20 mg/kg/day), or both according to a 2 x 2 factorial design (24 animals per group) from 120 days of age and during 120 days. As compared to corresponding untreated groups, metoprolol significantly decreased mean blood pressure (-7%), and metoprolol and spironolactone significantly increased cardiac output (18% and 19%, respectively), mesenteric blood flow (11% and 14%), and femoral blood flow (13% and 17%), and significantly decreased systemic (-24% and -15%), mesenteric (-14% and -13%) and femoral (-19% and -10%) vascular resistances. Metoprolol significantly increased renal blood flow (22%) and significantly decreased renal vascular resistance (-23%). Metoprolol and spironolactone significantly decreased the cavity area of the left ventricle (-21% and -32%, respectively) and the collagen density of the left (-36% and -39%) and right (-38% and -43%) ventricles. Although the combination did not induce stronger effects than each drug alone on the systemic and most regional hemodynamic variables, it did have a stronger effect on the cardiac remodeling (compared to control group: -24%, -34%, and -46% for the left ventricle cavity area, -33%, -35%, and -62% for collagen density in the left ventricle, and -52%, -57%, and -59% for collagen density in the right ventricle, respectively, in the metoprolol, spironolactone, and metoprolol + spironolactone groups). In CMH, metoprolol and spironolactone combined did not improve hemodynamics more than each drug alone, but did exert additive effects on cardiac remodeling.
Authors:
Sonia Goineau; Danielle Pape; Pascal Guillo; Marie-Paule Ramée; Eric Bellissant
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  40     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-27     Completed Date:  2003-03-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  543-53     Citation Subset:  IM    
Affiliation:
Laboratoire de Pharmacologie Expérimentale et Clinique, UPRES EA 3194, Groupe de Recherche Cardio-Vasculaire, Faculté de Médecine, Rennes, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiomyopathy, Dilated / drug therapy*,  physiopathology
Cricetinae
Drug Therapy, Combination
Hemodynamics / drug effects,  physiology
Male
Metoprolol / pharmacology,  therapeutic use*
Spironolactone / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
37350-58-6/Metoprolol; 52-01-7/Spironolactone

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


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