© 2002 European Society of Cardiology
Effects of diuretic treatment on cardiac and circulating RAS in chronic heart failure post-myocardial infarction in rats
a Med. Klinik und Poliklinik der Universität des Saarlandes, Innere Medizin III, Kardiologie und Angiologie 66421 Homburg/Saar, Germany
b Kinki University Nara Hospital, Cardiovascular Medicine Otoda, 1248-1 Ikoma, Japan
c Institut für Experimentelle und Klinische Pharmakologie und Toxikologie Universität Erlangen-Nürnberg Erlangen-Nürnberg, Germany
d Aventis Pharma, DG Cardiovascular Research 65926 Frankfurt/Main, Germany
* Corresponding author. Tel.: +49-6841-162-3372; fax: +49-6841-162-3369. E-mail address: boehm{at}med-in.uni-sb.de (M. Böhm), seeland{at}med-in.uni-sb.de (U. Seeland).
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Abstract |
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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.
Key Words: SHR, spontaneously hypertensive rats • RAS, renin–angiotensin system • LV, left ventricle or left ventricular
Received March 27, 2002; Revised August 30, 2002; Accepted September 2, 2002
1 Contributed equally to the article.
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