title: Demonstration of altered fibroblast contractile activity in hypertensive heart disease.
abstract: OBJECTIVE
  The aim of this study is to investigate the idea that altered fibroblast contractile activity is involved in the pathogenesis of hypertensive heart disease (HHD).
  
  
  METHODS
  Cell area and contraction are quantified using the traction force microscopy technique for cardiac fibroblasts isolated from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats.
  
  
  RESULTS
  The data indicate that there are marked phenotypic differences between the two cell types. For instance, WKY fibroblasts exert an average traction stress of approximately 3.3 kPa and have an area of approximately 2640 microm(2). Under identical conditions the SHR fibroblasts have an area approximately 1.45 times larger (p<0.01) and exert an average stress approximately 1.86 times higher (p<0.01). Challenging WKY fibroblasts with 1 micromol/l angiotensin II (Ang II) gradually causes a approximately 2-fold increase in traction after 1 h while simultaneously causing a approximately 28% decrease in area. In contrast, Ang II has no effect on SHR fibroblasts. The data also show that WKY and SHR cells respond in different ways when challenged with irbesartan (Irb). The addition of 1 micromol/l Irb initially causes WKY cells to decrease their average traction output by approximately 50% after approximately 10 min. Subsequently, contractile activity begins to recover and returns to normal after 1 h. The SHR cells also decrease their tractions by approximately 50%, but this decrease requires 30 min for completion and there is no recovery to the initial contractile state. For both cell types, Irb produces no significant effect on area and the combined effect of equimolar Irb and Ang II is the same as Irb alone.
  
  
  CONCLUSIONS
  These in vitro data suggest that among the many factors producing hypertensive heart disease in SHR's are excessive contraction of their cardiac fibroblasts and defective control of fibroblast contraction by Ang II.
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Marganski
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: De Biase
authors.forename: Maria L
authors.initials: ML
authors.lastname: Burgess
authors.forename: Micah
authors.initials: M
authors.lastname: Dembo
mesh_terms: D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D005347:Fibroblasts / Q000473:pathology; D006973:Hypertension / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014143:Traction