Effects of Calcimimetic Combined with an Angiotensin-Converting Enzyme Inhibitor on Uremic Cardiomyopathy Progression

Abstract

Background/Aims: Angiotensin-converting enzyme (ACE) inhibitors have cardioprotective properties and functional calcium-sensing receptors express in cardiac myocytes. Methods: Rats were made uremic by 5/6 nephrectomy and treated as follows: uremic rats were fed on a regular diet (UC), uremic + enalapril (E), uremic + calcimimetic agent R-568 (R-568), and uremic + enalapril + R-568 (E+R-568). A group of normal rats served as controls (NC). Results: Blood pressure (BP) and left ventricle mass were elevated significantly in the UC and R-568 groups compared with those in the NC group, but were indistinguishable from normal controls in the E and E+R-568 groups. Cardiac fibrosis was significantly increased in the UC group compared with that in the NC group. This increase was significantly attenuated in the R-568 and E groups, and the attenuation was further enhanced in the E+R-568 group. Factors associated with cardiac hypertrophy such as proliferating cell nuclear antigen, cyclin D1, and cyclin D2, as well as factors associated with cardiac fibrosis such as type I collagen, fibronectin, and transforming growth factor-β1 were significantly increased in the UC group compared with those in the NC group. Monotherapy with R-568 or E attenuated this increase and the combination further attenuated these measures. Conclusions: Calcimimetics can suppress the progression of uremic cardiomyopathy and this effect is amplified when BP is controlled via renin-angiotensin system blockade.