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Updated: Sep 25, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Effects of diuretic treatment on cardiac and circulating RAS in chronic heart failure post-myocardial infarction in
Ute Seeland1, Ichiro Kouchi, Oliver Zolk
1Innere Medizin III, Kardiologie und Angiologie,Med. Klinik und Poliklinik der Universität des Saarlandes, 66421 Homburg/Saar, Germany. seeland@med-in.uni-sb.de
Insights
Diuretic treatment, like furosemide, benefits heart failure by reducing cardiac angiotensin converting enzyme (ACE) and remodeling, even when combined with ACE inhibitors.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Heart Failure Pathophysiology
Background:
- Cardiac angiotensin converting enzyme (ACE) activation by wall stress drives cardiac remodeling.
- Heart failure management often involves ACE inhibitors and diuretics, but diuretics may activate the renin-angiotensin system (RAS).
Purpose of the Study:
- To investigate the impact of diuretic therapy on cardiac and circulating RAS in rats with chronic heart failure post-myocardial infarction.
Main Methods:
- Myocardial infarction induced in spontaneously hypertensive rats.
- Rats received ramipril, furosemide, or combination therapy for six weeks post-infarction.
Main Results:
- All treatments reduced right ventricular hypertrophy and improved left ventricular systolic function.
- Cardiac ACE mRNA and activity increased in untreated rats, attenuated by ramipril and furosemide.
- Furosemide and ramipril alone inhibited cardiac ACE activity increase; combination therapy further depressed it.
Conclusions:
- Furosemide and ramipril effectively reduce cardiac ACE and remodeling in post-infarction heart failure.
- Diuretics offer benefits without interfering with ACE inhibitor efficacy.
- Reduced wall stress from decreased volume overload may explain diuretic effects on cardiac ACE in hypertensive hearts.
Background:
Cardiac angiotensin converting enzyme (ACE) is activated by an increase in wall stress and is involved in remodeling processes. Heart failure is often treated with ACE inhibitors and diuretics although diuretic treatment could activate the renin-angiotensin system (RAS).
Aims:
To examine the effects of diuretic treatment on cardiac and circulating RAS in post-infarction chronic heart failure.
Methods:
Myocardial infarction was produced by coronary artery ligation in spontaneously hypertensive rats. The rats were randomly assigned to receive either ramipril (1 mg/kg/day), furosemide (4 mg/kg/day), or combination therapy for 6 weeks, commencing 2 weeks after infarction.
Results:
All three treatment protocols equivalently attenuated reactive hypertrophy of the right ventricle and ventricular septum and improved left ventricular systolic function. Both cardiac ACE mRNA and activity were significantly increased in untreated rats. This increase was attenuated by both ramipril and furosemide and further depressed by the combination. The increase in activity was completely inhibited by either agent alone. Plasma renin activity was upregulated by ramipril or ramipril plus furosemide but not influenced by infarction or furosemide alone.
Conclusions:
Furosemide and ramipril significantly reduced cardiac ACE and remodeling. Diuretics work favorably and do not interfere with the effects of ACE inhibitors. Possibly, a reduction in wall stress due to decreased volume overload accounts for the effects of diuretics on cardiac ACE in the treatment of post-infarction remodeling in hypertensive hearts. These data suggest a new mechanism for the frequently observed beneficial effect of diuretics in heart failure.
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