title: Effects of diuretic treatment on cardiac and circulating RAS in chronic heart failure post-myocardial infarction in rats.
abstract: 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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Innere Medizin III, Kardiologie und Angiologie,Med. Klinik und Poliklinik der Universität des Saarlandes, 66421 Homburg/Saar, Germany. seeland@med-in.uni-sb.de
authors.forename: Ute
authors.initials: U
authors.lastname: Seeland
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kouchi
authors.forename: Oliver
authors.initials: O
authors.lastname: Zolk
authors.forename: Friedrich
authors.initials: F
authors.lastname: Jockenhövel
authors.forename: Gabi
authors.initials: G
authors.lastname: Itter
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Linz
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D008297:Male; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D010919:Placebos; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017257:Ramipril / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013223:Statistics as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D010919:Placebos; D012333:RNA, Messenger; D005665:Furosemide; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril