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The cardiac renin-angiotensin system in heart failure
C I Johnston1, B Fabris, K Yoshida
1Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Insights
Angiotensin-converting enzyme (ACE) inhibitors benefit heart failure by reducing cardiac ACE activity. This suppression aids in preventing ventricular remodeling and improving survival rates.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Angiotensin-converting enzyme (ACE) inhibitors reduce cardiovascular events.
- The renin-angiotensin system (RAS) plays a role in cardiovascular pathophysiology.
- Cardiac dysfunction involves neurohumoral activation, with late increases in plasma renin and aldosterone.
Purpose of the Study:
- To investigate the role of the local cardiac renin-angiotensin system in heart failure.
- To examine the effects of ACE inhibitors on cardiac ACE activity and ventricular remodeling.
Main Methods:
- Experimental myocardial infarction in rats.
- Measurement of plasma and myocardial ACE activity.
- Assessment of hemodynamic parameters, neurohumoral activation, and ventricular remodeling post-treatment with ACE inhibitors.
Main Results:
- Myocardial ACE activity significantly increased after experimental myocardial infarction, despite normal plasma renin and aldosterone levels.
- ACE inhibitor treatment suppressed cardiac ACE, improved hemodynamics, reversed neurohumoral activation, prevented ventricular dilatation and remodeling, and reduced mortality.
Conclusions:
- The beneficial effects of ACE inhibitors in heart failure may involve suppressing the local cardiac renin-angiotensin system, in addition to reducing preload and afterload.
- Targeting cardiac ACE offers a potential therapeutic strategy for congestive cardiac failure and ventricular remodeling.
Abstract:
The success of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular morbidity and mortality rates has led to a reexamination of the role of the renin-angiotensin system in pathophysiology. Ventricular dysfunction leading to congestive cardiac failure is associated with sequential activation of the sympathetic system and increases in plasma atrial natriuretic peptide; however, increases in plasma renin and aldosterone do not occur until very late. The renin-angiotensin system is now regarded as both a circulating and tissue hormonal system. All components of the renin-angiotensin system have been detected in the heart. ACE is localized in discrete areas of the heart, including the cardiac valves, coronary vessels, atria, and myocardium. After experimental myocardial infarction in the rat, although plasma renin and aldosterone levels are not increased, ACE in the myocardium is markedly increased. Treatment with ACE inhibitors suppresses cardiac ACE and is associated with hemodynamic improvement, reversal of the neurohumoral activation, prevention of ventricular dilatation, and remodeling and reduction in mortality rates. These results suggest that the beneficial effects of ACE inhibitors in treating congestive cardiac failure, preventing ventricular remodeling, and regressing left ventricular hypertrophy may involve not only reducing preload and afterload but also suppressing the local cardiac renin-angiotensin system.