title: Angiotensin-II receptor blocker exerts cardioprotection in diabetic rats exposed to hypoxia.
abstract: BACKGROUND
  Hypoxia caused by sleep apnea might be associated with an increased risk of cardiovascular events in subjects with metabolic syndrome. The aim of this study was to examine the effect of hypoxia on the left ventricular (LV) myocardium and evaluate the cardioprotective effect of an angiotensin-II receptor blocker (ARB) in diabetic rats.
  
  
  RESULTS
  Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 30 weeks of age (n=30) were divided into 2 groups that were treated with vehicle or candesartan 0.2 mg x kg(-1) x day (-1). The animals were housed in a hypoxic gas chamber (oxygen, 10.0+/-0.5%, mean +/- standard deviation) for 2 weeks. Hypoxia increased right ventricular (RV) systolic pressure (hypoxia; 78+/-14 mmHg vs control; 22+/-5, p<0.05), but did not increase LV systolic pressure (131+/-23 mmHg vs 121+/-10). Hypoxia exacerbated the degeneration of cardiomyocytes, and accelerated the expression of hypoxia inducible factor-1alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in the myocardium. Treatment with ARB decreased RV and LV pressures (46+/-7 and 100+/-18 mmHg, respectively), suppressed the expression of HIF-1alpha and VEGF, and preserved the fine structure of the LV myocardium.
  
  
  CONCLUSIONS
  ARB exhibited cardioprotection under hypoxia, in part through the reduction of blood pressure and cytokine expression, in OLETF rats. Thus, ARB might be a potent agent for the treatment of diabetic patients with the complication of sleep apnea.
authors.affiliation: Third Department of Medicine, Osaka Medical College, Takatsuki, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Inamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Tazawa
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Mori
authors.forename: Chika
authors.initials: C
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Sohmiya
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakai
authors.forename: Eisuke
authors.initials: E
authors.lastname: Furuya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D013777:Tetrazoles / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C081643:candesartan