title: Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy.
abstract: OBJECTIVE
  This study aimed to characterize the difference between renin angiotensin system (RAS)-dependent and RAS-independent hypertrophy and their differential contribution to the transition to heart failure.
  
  
  BACKGROUND
  Hypertensive left ventricular (LV) hypertrophy develops with RAS activation in the heart; however, LV hypertrophy develops even without RAS activation.
  
  
  METHODS
  Left ventricular geometry and function were assessed in Dahl salt-sensitive rats placed on an 8% NaCl diet from seven weeks old (hypertensive rats) and in those placed on an 0.3% NaCl diet (control rats, n = 8). The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study.
  
  
  RESULTS
  From 7 to 13 weeks, AT1R blockade at a subdepressor dose did not restrain the development of LV hypertrophy but prevented narrowing of LV diastolic dimension, leading to the normalization of abnormally decreased end-systolic wall stress in the untreated rats. Progressive development of LV hypertrophy in spite of lower than normal end-systolic wall stress (excessive hypertrophy) after 13 weeks was suppressed by the AT1R blockade. Elevation of LV end-diastolic pressure and prolongation of Tau were associated with histological evidence of myocyte hypertrophy and massive interstitial fibrosis in the untreated rats, and none of these was evident in the treated rats.
  
  
  CONCLUSIONS
  Renin-angiotensin system activation and AT1R signaling may be dispensable for the development of early adaptive LV hypertrophy and closely linked to the transition to heart failure.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: T
authors.initials: T
authors.lastname: Masuyama
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: R
authors.initials: R
authors.lastname: Doi
authors.forename: T
authors.initials: T
authors.lastname: Mano
authors.forename: T
authors.initials: T
authors.lastname: Kuzuya
authors.forename: T
authors.initials: T
authors.lastname: Miwa
authors.forename: H
authors.initials: H
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D012084:Renin-Angiotensin System / Q000502:physiology*