Document Detail


Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension.
MedLine Citation:
PMID:  8421998     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of the renin-angiotensin-aldosterone system in arterial hypertension can lead to remodeling of the myocardial collagen network, with progressive collagen accumulation in the cardiac interstitium. This reactive myocardial fibrosis, which is not secondary to myocyte necrosis, appears to be an important determinant of diastolic dysfunction and thus of pathologic hypertrophy. To examine the effects of the aldosterone antagonist spironolactone on myocardial fibrosis, we analyzed interstitial fibrosis in 7 different models of arterial hypertension in rats: 2 kidney, 1 clip model of renovascular hypertension (RHT); continuous subcutaneous aldosterone (0.75 micrograms/hr) infusion; RHT and aldosterone models treated with 20 mg/kg per day of subcutaneous spironolactone; uninephrectomized rats on a high sodium diet; and age- and sex-matched controls with or without spironolactone treatment. Systolic arterial pressure was comparably elevated in RHT and aldosterone models; it was modestly lowered but not normalized by 8 weeks of spironolactone treatment at the low doses used. Such treatment also failed to prevent left ventricular hypertrophy (LVH) in all experimental groups with hypertension. Spironolactone, however, was able to prevent myocardial fibrosis in RHT and aldosterone models of acquired arterial hypertension irrespective of the development of LVH and the presence of hypertension. These findings provide further evidence that elevated aldosterone levels play an important role in the adverse remodeling of the myocardium in arterial hypertension. The antifibrotic effects of spironolactone, if confirmed in human studies, may be a valuable strategy in treating hypertensive heart disease.
Authors:
C G Brilla; L S Matsubara; K T Weber
Related Documents :
15018248 - Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrog...
16980198 - Cortisol metabolism in hypertension.
1188918 - Renal effects of prostaglandin e1 in hypertensive patients.
19593208 - Cyp2c9 genotype modifies activity of the renin-angiotensin-aldosterone system in hypert...
20634018 - An impedance threshold device increases blood pressure in hypotensive patients.
11061328 - Research on red cell membrane permeability in arterial hypertension.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of cardiology     Volume:  71     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  1993 Jan 
Date Detail:
Created Date:  1993-02-18     Completed Date:  1993-02-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  12A-16A     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, Philipps University of Marburg, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aldosterone / blood
Angiotensin II / blood
Animals
Cardiomyopathies / etiology,  pathology,  prevention & control*
Fibrosis / etiology,  prevention & control
Hyperaldosteronism / complications
Hypertension / complications*,  metabolism
Hypertension, Renovascular / complications
Male
Potassium / urine
Rats
Rats, Sprague-Dawley
Sodium / urine
Spironolactone / therapeutic use*
Grant Support
ID/Acronym/Agency:
R01-31701//PHS HHS
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 7440-09-7/Potassium; 7440-23-5/Sodium

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


Previous Document:  Effects of successful cardiac transplantation on plasma endothelin.
Next Document:  Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate ess...