title: VEGF-mediated angiogenesis is impaired by angiotensin type 1 receptor blockade in cardiomyopathic hamster hearts.
abstract: OBJECTIVE
  Coronary microcirculation plays an important role in the progression of cardiac remodeling. Among angiogenic factors, it has been reported that angiotensin II may contribute to neovascularization. However, it is unknown whether inhibition of the renin-angiotensin system suppresses angiogenesis, especially within the heart. Our aim was to evaluate the effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor type I blocker valsartan on cardiac microvasculature, function, vascular endothelial growth factor (VEGF) expression, and survival in cardiomyopathic hamsters.
  
  
  METHODS
  Male cardiomyopathic hamsters (BIO TO2) were administered either a placebo (group C), enalapril (30 mg/kg/day) (group E), or valsartan (40 mg/kg/day) (group V), starting at the age of 6 weeks. This continued until death. Hemodynamic study, histological analysis, and northern blot analysis were performed at 39 weeks.
  
  
  RESULTS
  Group V showed significant increases in percent fibrosis, end diastolic pressure, and LV dP/dt min, and significant decreases in percent fractional shortening, LV dP/dt max, capillary density, and the level of mRNA expression of VEGF compared with group C. Group E showed significant increases in percent fractional shortening while the capillary density and level of mRNA expression of VEGF were unchanged. The 300-day survival rate was significantly lower in group V (25.0%) but higher in group E (100%) than that of group C (66.7%).
  
  
  CONCLUSIONS
  Therapy with valsartan may have adverse effects on survival rate concomitant with the progression of cardiac remodeling owing to impaired VEGF-mediated angiogenesis. Therapy with enalapril has a neutral effect on VEGF-mediated angiogenesis, leading to the suppression of cardiac remodeling and an increase in life expectancy.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Chiba
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Akino
authors.forename: Jia
authors.initials: J
authors.lastname: Nan
authors.forename: Hideki
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Hisao
authors.initials: H
authors.lastname: Onozuka
authors.forename: Taisei
authors.initials: T
authors.lastname: Mikami
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D006224:Cricetinae; D004656:Enalapril / Q000627:therapeutic use*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D008222:Lymphokines / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004656:Enalapril; D000068756:Valsartan; D014633:Valine