title: Ramipril prevents extracellular matrix accumulation in cerebral microvessels.
abstract: OBJECTIVE
  The stroke-prone spontaneously hypertensive rat is a genetic model of severe hypertension with secondary vascular alterations. The aim of this study was to determine the influence of chronic hypertension and ramipril treatment on the extracellular matrix in the cerebral microvasculature.
  
  
  METHODS
  The study consisted of three groups: six normotensive Wistar rats, six untreated spontaneously hypertensive rats, and six hypertensive rats treated with an antihypertensive dose of ramipril (1 mg kg(-1)day(-1)) for 6 months. Alterations in the extracellular matrix were examined by western blot, immunohistochemistry, and immunofluorescence using an antibody against collagen type IV.
  
  
  RESULTS
  Western blotting showed a reduction of the total amount of collagen type IV by 50% in the ramipril group compared with the untreated hypertensive group (51.0+/-9.3% reduction, p = 0.0004). Compared with the untreated hypertensive rats, ramipril treatment prevented a loss of vessel density in the cortex (23.4+/-1.0 versus 20.4+/-2.0, p < 0.0001) and revealed a reduction of the amount of collagen per vessel (0.54+/-0.04 versus 0.60+/-0.08, p = 0.037). The ratio between the vessel wall and the lumen (0.69+/-0.08 versus 1.31+/-0.13) and the relative collagen intensity was lowered in the ramipril group (18.1+/-4.7% reduction, p < 0.0001). Using these methods the ramipril group showed similar results than the normotensive group.
  
  
  CONCLUSIONS
  Ramipril treatment completely prevented these hypertensive vascular changes. These results may stimulate a therapeutic approach with angiotensin converting enzyme inhibition in human hypertensive small vessel disease.
authors: Department of Neurology, Dr. Horst Schmidt Klinik, Ludwig-Erhard Str. 100, 65199 Wiesbaden, Germany. martin.liebetrau@hsk-wiesbaden.de
authors: Martin
authors: M
authors: Liebetrau
authors: Dorothe
authors: D
authors: Burggraf
authors: Christine
authors: C
authors: Büscher
authors: Wolfgang
authors: W
authors: Linz
authors: Gerhard F
authors: GF
authors: Hamann
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western / Q000379:methods; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism*; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D017257:Ramipril / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D024141:Collagen Type IV; D017257:Ramipril