title: Effects of calcimimetic combined with an angiotensin-converting enzyme inhibitor on uremic cardiomyopathy progression.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. mizobu@med.showa-u.ac.jp
authors.forename: Masahide
authors.initials: M
authors.lastname: Mizobuchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ogata
authors.forename: Nozomu
authors.initials: N
authors.lastname: Hosaka
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kumata
authors.forename: Ai
authors.initials: A
authors.lastname: Nakazawa
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kondo
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Koiwa
authors.forename: Eriko
authors.initials: E
authors.lastname: Kinugasa
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000814:Aniline Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002118:Calcium / Q000819:agonists; D009202:Cardiomyopathies / Q000209:etiology* / Q000517:prevention & control*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010627:Phenethylamines; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000150:complications*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D011437:Propylamines; D004656:Enalapril; D002118:Calcium