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Combined effects of low-dose spironolactone and captopril therapy in a rat model of genetic hypertrophic cardiomyopathy. J Cardiovasc Pharmacol 2006 Dec;48(6):265-73

Date

01/06/2007

Pubmed ID

17204904

DOI

10.1097/01.fjc.0000248236.43760.86

Abstract

For several years, the severe side effects associated with the use of high doses of the aldosterone antagonist, spironolactone, limited its clinical use. Studies have recently shown efficacy and minimal side effects of low-dose spironolactone combined with standard therapy in the treatment of heart failure and hypertensive patients. The authors evaluated the effects of low-dose spironolactone alone or in combination with angiotensin-converting enzyme (ACE) inhibitors on the progression of left ventricular dysfunction and remodeling in a congenic rat model of hypertrophic cardiomyopathy. The congenic SS-16/Mcwi rats developed severe cardiac hypertrophy despite being normotensive even on high-salt diet. SS-16/Mcwi and SS/Mcwi rats were fed a low-salt (0.4% NaCl) diet and were treated with vehicle (CON), spironolactone (20 mg/kg/d subcutaneously), captopril (100 mg/kg/d drinking water), or both spironolactone and captopril for 4 weeks. Blood pressure, plasma peptides, cardiac fibrosis, and echocardiography measurements were evaluated. Spironolactone at a low dose had no effect on blood pressure, cardiac hypertrophy, and fibrosis in either strain. However, in combination with captopril, spironolactone decreased the cardiac hypertrophy more than captopril treatment alone. In the SS-16/Mcwi rats, the combined therapy significantly preserved the cardiac index when compared with control. These data indicate that the addition of low-dose spironolactone to captopril treatment was more effective in preventing the progression of heart hypertrophy and ventricular dysfunction in the SS-16/Mcwi than captopril alone. This study suggests that combined spironolactone and captopril therapy may be useful in the treatment of hypertrophic cardiomyopathy.

Author List

de Resende MM, Kriegel AJ, Greene AS

Author

Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Oral
Aldosterone
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Animals
Animals, Congenic
Atrial Natriuretic Factor
Blood Pressure
Captopril
Cardiomyopathy, Hypertrophic
Disease Models, Animal
Diuretics
Dose-Response Relationship, Drug
Drug Therapy, Combination
Echocardiography
Injections, Subcutaneous
Myocardium
Organ Size
Random Allocation
Rats
Rats, Inbred Strains
Spironolactone
Ventricular Function, Left
Weight Loss
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d