Long-term treatment with trandolapril opposes cardiac remodeling and prolongs survival after myocardial infarction in rats.
Long-term treatment with angiotensin I converting enzyme inhibitors (ACEIs) prolongs survival in rats developing congestive heart failure after myocardial infarction (MI). In this experimental model, we investigated at regular intervals the effects of a 1-year oral treatment with trandolapril, a new ACEI, on (a) survival rate and duration and (b) hemodynamic, biological, and cardiac and vascular histomorphological parameters. Control MI rats and sham-operated trandolapril-treated and control rats were simultaneously studied. In MI rats, trandolapril significantly increased the survival rate and duration, increasing the life expectancy by approximately 6 months. It also significantly decreased the arterial blood pressure and increased diuresis. These effects occurred as soon as the treatment was started and persisted throughout the study. Trandolapril significantly limited the development of myocardial hypertrophy, decreasing the heart weight and left ventricular hypertrophic area and increasing the left ventricular myocyte nuclear density, but these effects, starting after 3-6 months, were delayed compared to the hemodynamic ones. Finally, trandolapril limited the development of myocardial (both subendocardial and subepicardial) and aortic fibrosis. It is concluded that the early pre- and afterload effects of trandolapril are initially responsible for its beneficial action on survival, whereas later the drug's antihypertrophic and antifibrotic properties together with persistent hemodynamic effects account for the prolonged survival improvement.
Richer
C
C
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Mulder
P
P
Fornes
P
P
Domergue
V
V
Heudes
D
D
Giudicelli
J F
JF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D004231:Diuresis / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril