title: Angiotensin-converting enzyme inhibition promotes coronary angiogenesis in the failing heart of Dahl salt-sensitive hypertensive rats.
abstract: BACKGROUND
  The biologic response to angiotensin-converting enzyme (ACE) inhibitors may be influenced by the local environment. The effect of ACE inhibition on coronary angiogenesis was investigated in a rat model of hypertensive heart failure.
  
  
  RESULTS
  Dahl salt-sensitive (DS) rats fed a high-salt diet from 6 weeks of age were treated with a nonantihypertensive dose of the ACE inhibitor perindopril or vehicle from 9 to 18 weeks. Treatment of rats with perindopril attenuated the heart failure as well as cardiac hypertrophy and fibrosis that were manifest in the vehicle-treated animals. Myocardial capillary density as well as the expression of the bradykinin B(2) receptor, endothelial nitric oxide synthase, and vascular endothelial growth factor were reduced in the heart of vehicle-treated rats compared with that of nonhypertensive control rats, and all of these changes were attenuated by treatment with perindopril.
  
  
  CONCLUSIONS
  These results indicate that ACE inhibition by perindopril promotes myocardial capillary formation as well as attenuates cardiac remodeling and failure in a manner independent from the antihypertensive effect of the drug in DS hypertensive rats. The beneficial cardiac effects of perindopril were associated with activation of the bradykinin-nitric oxide pathway in the heart.
authors: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hiroki
authors: H
authors: Yazawa
authors: Masaaki
authors: M
authors: Miyachi
authors: Mayuko
authors: M
authors: Furukawa
authors: Keiji
authors: K
authors: Takahashi
authors: Miwa
authors: M
authors: Takatsu
authors: Koji
authors: K
authors: Tsuboi
authors: Masafumi
authors: M
authors: Ohtake
authors: Tamayo
authors: T
authors: Murase
authors: Takuya
authors: T
authors: Hattori
authors: Yosuke
authors: Y
authors: Kato
authors: Toyoaki
authors: T
authors: Murohara
authors: Kohzo
authors: K
authors: Nagata
mesh_terms: D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D006352:Heart Ventricles; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000187:drug effects; D020913:Perindopril / Q000627:therapeutic use*; D051381:Rats; D020303:Rats, Inbred Dahl; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D020913:Perindopril