Effects of cariporide and losartan on hypertrophy, calcium transients, contractility, and gene expression in congestive heart failure.
BACKGROUND
The purpose of this study was to compare long-term effects of cariporide with those of losartan in postinfarction heart failure.


RESULTS
Female Sprague-Dawley rats with large myocardial infarctions and sham controls were randomized to losartan, cariporide, or placebo after 7 days and treated for 49 days. Cardiac function was assessed by echocardiography and measurement of left ventricular pressures, and gene expression was assessed by competitive reverse transcription-polymerase chain reaction. Cell dimensions, shortening, and relaxation were determined by videomicroscopy and calcium transients by fura 2. Losartan reduced postinfarction systolic and diastolic left ventricular dilation (by 24% and 31%, respectively), left and right ventricular weight (by 22% and 26%, respectively), and cardiomyocyte hypertrophy length and width (by 62% and 54%, respectively). Induction of myocardial atrial natriuretic peptide decreased 66%. Cariporide did not affect postinfarction hypertrophy or atrial natriuretic peptide. Losartan and cariporide respectively improved reduced cellular contractility (55% and 30%) and reduced elevated systolic (86% and 27%) and diastolic (49% and 43%) calcium. Losartan and cariporide respectively reduced prolonged time to 50% relaxation (66% and 25%) and time to 50% calcium reduction (55% and 53%).


CONCLUSIONS
Losartan and cariporide improve cardiomyocyte contractility and calcium regulation in chronic heart failure. Losartan has salutary effects on postinfarction remodeling and gene expression, whereas cariporide is neutral.
Loennechen
Jan P
JP
Department of Physiology and Biomedical Engineering, Norwegian University of Science and Technology, Trondheim, Norway.
Wisløff
Ulrik
U
Falck
Geir
G
Ellingsen
Oyvind
O
D000809:Angiotensins / Q000037:antagonists & inhibitors; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D006332:Cardiomegaly / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002469:Cell Separation; D048429:Cell Size / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D004558:Electric Stimulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects
D000809:Angiotensins; D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; C093373:cariporide; D019808:Losartan