title: Efficacy of olmesartan and nifedipine on recurrent hypoxia-induced left ventricular remodeling in diabetic mice.
abstract: OBJECTIVE
  Recurrent hypoxia due to sleep apnea syndrome is implicated in cardiovascular events, especially in diabetic patients, but the underlying mechanisms remain controversial. We previously reported that angiotensin II receptor blockers can improve hypoxia-induced left ventricular remodeling. The aim of this study was to examine the effect on left ventricular remodeling of adding a calcium channel blocker to angiotensin II receptor blocker therapy in diabetic mice exposed to recurrent hypoxia.
  
  
  METHODS
  Male db/db mice (8-week-old) and age-matched control db/+ mice were fed a Western diet and subjected to recurrent hypoxia (oxygen at 10+/-0.5% for 8h daily during the daytime) or normoxia for 3weeks. Hypoxic db/db mice were treated with the vehicle, olmesartan (3mg/kg/day), nifedipine (10mg/kg/day), or both drugs.
  
  
  RESULTS
  Recurrent hypoxia caused hypertrophy of cardiomyocytes, interstitial fibrosis, and a significant increase in expression of the oxidative stress marker 4-hydroxy-2-nonenal (4-HNE) in the left ventricular myocardium. Treatment with olmesartan, nifedipine, or both drugs had no effect on systolic blood pressure, and each treatment achieved similar suppression of 4-HNE expression. Olmesartan and the combination with olmesartan and nifedipine significantly prevented cardiomyocyte hypertrophy more than treatment with nifedipine alone. On the other hand, olmesartan combined with nifedipine significantly reduced cytokine expression, superoxide production and matrix metalloproteinase (MMP)-9 activity, and significantly suppressed interstitial fibrosis in the left ventricular myocardium.
  
  
  CONCLUSIONS
  The combination with olmesartan and nifedipine, as well as a monotherapy with olmesartan, exerts preferable cardioprotection in diabetic mice exposed to recurrent hypoxia.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Yamashita
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Mori
authors.forename: Chika
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Kento
authors.initials: K
authors.lastname: Kitada
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Miyamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Sohmiya
authors.forename: Akira
authors.initials: A
authors.lastname: Ukimura
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Okada
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009543:Nifedipine / Q000008:administration & dosage*; D055502:Secondary Prevention; D013777:Tetrazoles / Q000008:administration & dosage*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D004041:Dietary Fats; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D009543:Nifedipine