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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 PMID: 17204904


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


Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin
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
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Animals, Congenic
Atrial Natriuretic Factor
Blood Pressure
Cardiomyopathy, Hypertrophic
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Therapy, Combination
Injections, Subcutaneous
Organ Size
Random Allocation
Rats, Inbred Strains
Ventricular Function, Left
Weight Loss

View this publication's entry at the Pubmed website PMID: 17204904
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