Effects of Cariporide and Losartan on Hypertrophy, Calcium Transients, Contractility, and Gene Expression in Congestive Heart Failure

Abstract

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.

Superior Cardiovascular Effect of Aerobic Interval Training Versus Moderate Continuous Training in Heart Failure Patients

“…Aerobic interval training (AIT) involving periods at 90% of V O 2peak has been shown to rescue impaired cardiomyocyte contractility, attenuate myocardial hypertrophy, and reduce myocardial expression of atrial natriuretic peptide in a rat model of postinfarction heart failure. 9 The beneficial effects on cardiac remodeling and myocyte function were similar to those observed with the angiotensin II receptor blocker losartan, 10 which indicates that AIT might be a potent modifier of postinfarction heart failure. We therefore hypothesized that AIT is more effective than moderate continuous training (MCT) in enhancing cardiovascular fitness and reversing myocardial remodeling in patients undergoing optimal treatment for stable heart failure after a myocardial infarction.…”

Long-Term Serotonin Administration Induces Heart Valve Disease in Rats

“…Two-dimensional color-flow Doppler in the parasternal long-axis and apical views was used to visualize valvular regurgitation, which was confirmed by continuous-wave Doppler recordings. [22][23][24][25] Treatment group identity was unknown during echocardiography.…”

Na+–H+ exchanger inhibitor prevents early death in hereditary cardiomyopathy

“…This sodium overload could consequently lead to a calcium overload due to the increased activity of the sodium-calcium exchanger (NCX) (Chahine et al 2005;Baartscheer et al 2008). Studies using animal models of HF (Yoshida and Karmazyn 2000;Engelhardt et al 2002;Loennechen et al 2002;Chen et al 2004;Baartscheer et al 2008;Karmazyn et al 2008) as well as isolated cardiomyocytes (Karmazyn et al 2003) have demonstrated the beneficial effect of NHE-1 blockade in preventing cardiac hypertrophy. In addition, the levels of angiotensin II (Ang II), which is a hypertrophic factor and an indirect activator of NHE-1 (Karmazyn 2001), were elevated during the development of HF (Nakamura et al 1994).…”