title: Therapeutic effects of angiotensin II type 1 receptor blocker at an advanced stage of hypertensive diastolic heart failure.
abstract: OBJECTIVE
  Angiotensin II type 1 receptor blocker (ARB) is increasingly prescribed for the treatment of systolic heart failure with a growing body of clinical evidence. The roles of ARB, however, remain to be clarified in the treatment of diastolic heart failure (DHF), particularly at its advanced stage. This experimental study investigated the effects of ARB administered at an advanced stage of hypertensive DHF.
  
  
  METHODS
  Dahl salt-sensitive rats fed an 8% NaCl diet from age 7 weeks represent overt DHF at age 20 weeks, as noted in previous studies (hypertensive DHF model). The DHF model rats were randomly divided into two groups at age 17 weeks when left ventricular diastolic dysfunction, hypertrophy, fibrosis, macrophage infiltration and reactive oxygen species generation were already augmented; six rats treated for 3 weeks with a subdepressor dose of ARB (olmesartan 0.6 mg/kg per day), and six untreated rats.
  
  
  RESULTS
  The 3-week administration of ARB significantly decreased the left ventricular end-diastolic pressure in association with attenuation of left ventricular hypertrophy, fibrosis and diastolic dysfunction. Macrophage infiltration was attenuated with decreased gene expression of transforming growth factor-beta1 and monocyte chemoattractant protein-1 in the left ventricular myocardium of the ARB-treated rats. The production of reactive oxygen species also decreased with NADPH oxidase activity.
  
  
  CONCLUSIONS
  ARB provides beneficial effects in hypertensive DHF independent of its antihypertensive effects even if initiated at an advanced stage. The beneficial effects are at least partly attributed to the attenuation of inflammatory changes and oxidative stress through the suppression of cytokine and chemokine production and of NADPH oxidase activity.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Nishio
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshida
authors.forename: Tomohito
authors.initials: T
authors.lastname: Ohtani
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Takeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miwa
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy*; D006973:Hypertension / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D007249:Inflammation; D008297:Male; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D020303:Rats, Inbred Dahl; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018932:Chemokine CCL2; D007093:Imidazoles; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; C437965:olmesartan; D019255:NADPH Oxidases