Document Detail


Eplerenone decreases inflammatory foci in spontaneously hypertensive rat hearts with minimal effects on blood pressure.
MedLine Citation:
PMID:  19129737     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The blood pressure (BP)-lowering effects of mineralocorticoid receptor (MR) antagonists in salt-sensitive rat models of hypertension are well understood. However, studies in salt-independent models have yielded mixed results, and therefore, we measured the hemodynamic effects of MR blockade in spontaneously hypertensive rats. We treated spontaneously hypertensive rats for 8 weeks with 30-300 mg.kg.d eplerenone or 20 mg.kg.d losartan and monitored BP using radiotelemetry and performed histopathological analyses of the hearts. Eplerenone, in contrast to losartan, caused only a small reduction in systolic BP at the highest dose tested. Both reduced left ventricular wall thickness, although eplerenone was less effective than losartan. Only losartan decreased heart weight. We observed foci of cardiomyopathy characterized by combinations of infiltrating monocytes, necrotic myocytes, and interstitial fibrosis in hearts of control animals. The number of foci seemed to be decreased in hearts of losartan- and eplerenone-treated animals. In a second study, using quantitative histomorphometry, the number of foci was significantly reduced by 20 mg.kg.d losartan (by 68%) or by 300 mg.kg.d eplerenone (by 50%). Our data support the hypothesis that a direct BP-independent effect on the progression of cardiomyopathy in the heart may be one basis for the cardiac protection afforded by MR antagonism.
Authors:
Philip E Brandish; Thomas W Forest; Hongxing Chen; Nicholas T Gatto; Sylvain Molon-Noblot; Izabela Zwierzynski; Peter Szczerba; Gary E Adamson; Bennett K Ma; Osvaldo A Flores; James C Hershey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  53     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-20     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Heart / drug effects*,  physiopathology
Hypertension / blood,  drug therapy,  physiopathology
Losartan / pharmacology,  therapeutic use
Male
Rats
Rats, Inbred SHR
Sodium Chloride, Dietary / pharmacology,  therapeutic use
Spironolactone / analogs & derivatives
Chemical
Reg. No./Substance:
0/Sodium Chloride, Dietary; 27O7W4T232/Spironolactone; 6995V82D0B/eplerenone; JMS50MPO89/Losartan

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


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