Effects of cariporide and losartan on hypertrophy, calcium transients, contractility, and gene expression in congestive heart failure

Article

关键词: EXCHANGE INHIBITOR CARIPORIDE;    ISOLATED VENTRICULAR MYOCYTES;    REMODELED RAT-HEART;    SARCOPLASMIC-RETICULUM;    MYOCARDIAL-INFARCTION;    CARDIAC MYOCYTES;    DYSFUNCTION;    CAPTOPRIL;   

DOI  :  10.1161/hc1102.105258

来源: SCIE

【 摘 要 】

Background-The purpose of this study was to compare long-term effects of cariporide with those of losartan in postinfarction heart failure. Methods and 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.

【 授权许可】

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