title: Modulation of C16:0-ceramide in hypertrophied immature hearts by losartan.
abstract: BACKGROUND
  The angiotensin type 2 receptor plays a unique role in growth inhibition in adult myocardium via modulation of ceramide synthesis. Angiotensin type 1 (AT1 )-receptor blockade results in increased angiotensin type 2 receptor activation by angiotensin II, and AT1 -receptor blockers are sometimes prescribed to children for the treatment of cardiac hypertrophy or heart failure. We investigated the changes of ceramide lipid components in hypertrophied immature rabbit hearts after chronic administration of the AT1 -receptor blocker, losartan.
  
  
  METHODS
  One-week-old Japanese white rabbits were randomly divided into three groups: sham-operated control rabbits (Group S), rabbits given distilled water orally for 21 days after aortic constriction (Group H), and rabbits given losartan orally for 21 days after aortic constriction (Group H + L).
  
  
  RESULTS
  Compared with Group S, the hypertrophy index and left ventricular posterior wall thickness were significantly increased in Group H, but were not different in Group H + L. Total myocardial ceramide levels in Group H and Group H + L were suppressed compared with Group S. The relative fatty acid components of myocardial ceramide in Group H were the same as those in Group S, but Group H + L showed a significant increase in the C16 :0 component.
  
  
  CONCLUSIONS
  The total cardiac ceramide levels are depressed by pressure overload of immature rabbit hearts. Losartan reduced the hypertrophy with selective increase of the relative amount of C16:0 -ceramide.
authors: Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. titoi@koto.kpu-m.ac.jp
authors: Toshiyuki
authors: T
authors: Itoi
authors: Tatsujiro
authors: T
authors: Oka
authors: Naoto
authors: N
authors: Terada
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001024:Aortic Valve Stenosis / Q000473:pathology; D006332:Cardiomegaly / Q000473:pathology*; D002518:Ceramides / Q000032:analysis*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002518:Ceramides; C097760:N-palmitoylsphingosine; D019808:Losartan