Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation.

Abstract

The efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of chronic aortic regurgitation (AR) is not well established and remains controversial. The mechanisms by which ACEIs may protect against left-ventricular (LV) volume overload are not well understood, and clinical trials performed until now have yielded conflicting results. This study was therefore performed to assess the effectiveness of two different doses of the ACEI captopril in a rat model of chronic AR. We compared the effects of a 6-month low-dose (LD) (25 mg/kg) or higher dose (HD) (75 mg/kg) treatment with captopril on LV function and hypertrophy in Wistar rats with severe AR. Untreated animals developed LV eccentric hypertrophy and systolic dysfunction. LD treatment did not prevent hypertrophy and provided modest protection against systolic dysfunction. HD treatment preserved LV systolic function and dimensions and tended to slow hypertrophy. The cardiac index remained high and similar among all AR groups, treated or not. Tissue renin-angiotensin system (RAS) analysis revealed that ACE activity was increased in the LVs of AR animals and that only HD treatment significantly decreased angiotensin II receptor mRNA levels. Fibronectin expression was increased in the LV or AR animals, but HD treatment almost completely reversed this increase. The ACE inhibitor captopril was effective at high doses in this model of severe AR. These effects might be related to the modulation of tissue RAS and the control of fibrosis.

• Authors: Eric Plante, Martin Gaudreau, Dominic Lachance, Marie-Claude Drolet, Elise Roussel, Cindy Gauthier, Evelyne Lapointe, Marie Arsenault, Jacques Couet
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 82 Issue 3 Pg. 191-9 (Mar 2004) ISSN: 0008-4212 [Print] Canada
• PMID: 15052285 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Fibronectins
• RNA, Messenger
• Receptors, Angiotensin
• Captopril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Aortic Valve Insufficiency (complications, drug therapy)
• Captopril (pharmacology, therapeutic use)
• Cardiac Output (drug effects, physiology)
• Cardiomyopathy, Dilated (complications, drug therapy, prevention & control)
• Chronic Disease
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fibronectins (drug effects, genetics, metabolism)
• Gene Expression
• Hypertrophy, Left Ventricular (drug therapy, genetics)
• Male
• RNA, Messenger (chemistry, metabolism)
• Rats
• Rats, Wistar
• Receptors, Angiotensin (genetics, metabolism)
• Renin-Angiotensin System (drug effects)
• Stroke Volume (drug effects, physiology)
• Time Factors
• Ventricular Function, Left (drug effects, physiology)
• Ventricular Remodeling (drug effects)