title: Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in pressure-overloaded mice.
abstract: OBJECTIVE
  The effects of long-acting calcium channel blockers (CCBs) on pressure overload-induced cardiac remodeling are seldom studied in animals. We evaluated the effects of benidipine, a long-acting CCB, on cardiac remodeling.
  
  
  METHODS
  Rat neonatal cardiac myocytes were used to examine the influence of benidipine on protein synthesis. Cardiac remodeling was induced in C57 B6/J mice by transverse aortic constriction (TAC). Then the effects of benidipine (10 mg/kg/d) were assessed on myocardial hypertrophy and heart failure, cardiac histology, and gene expression.
  
  
  RESULTS
  Benidipine significantly inhibited protein synthesis by cardiac myocytes stimulated with phenylephrine (PE), and this effect was partially abolished by cotreatment with a nitric oxide synthase (NOS) inhibitor [N(G)-nitro-l-arginine methylester (l-NAME)]. Four weeks after the onset of pressure overload, benidipine therapy potently inhibited cardiac hypertrophy and prevented heart failure. The heart to body weight ratio was 6.89+/-0.48 mg/g in treated mice vs. 8.76+/-0.33 mg/g in untreated mice (P<0.01), and the lung to body weight ratio was 7.39+/-0.93 mg/g vs. 10.53+/-0.99 mg/g, respectively (P<0.05). Left ventricular fractional shortening (LVFS) was improved on echocardiography. Plasma NO levels were increased, while B type natriuretic peptide, protein inhibitor of neuronal NOS, and procollagen IV alpha were down-regulated in benidipine-treated mice.
  
  
  CONCLUSIONS
  These results indicate that benidipine inhibits cardiac remodeling due to pressure overload at least partly by acting on the nitric oxide signaling pathway.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0781, Japan.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Akiko
authors.initials: A
authors.lastname: Ogai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D002121:Calcium Channel Blockers; D024141:Collagen Type IV; D004095:Dihydropyridines; D009124:Muscle Proteins; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; C061004:benidipine