title: Increased collagen, per se, may not affect left ventricular function in spontaneously hypertensive rats.
abstract: BACKGROUND
  Left ventricular fibrosis is considered to be a major participant in the development of cardiac dysfunction in various conditions (hypertension, aging, etc). Because cardiac myocytes as well as blood supply may also be affected in these conditions, it is difficult to define quantitatively the role of fibrosis. We hypothesized that by inducing myocardial collagen accumulation by treatment with an inhibitor (doxycycline) of matrix metalloproteinases, which by itself should not affect cardiac myocytes, we might examine a more specific role of fibrosis in cardiac dysfunction.
  
  
  METHODS
  Adult male spontaneously hypertensive rats were divided into 2 groups. The control group received no treatment; the second group was given doxycycline (30 mg/kg/day) for 6 months. Arterial pressure, pulse wave velocity, indexes of heart function (end-diastolic pressure, maximal rates of pressure rise and fall [dP/dt(max) and dP/dt(min)], diastolic time constant [Tau]), weight indexes, and myocardial collagen concentration were determined at the end.
  
  
  RESULTS
  The results demonstrated that treatment with an inhibitor of matrix metalloproteinases induced significant accumulation of ventricular collagen, as indicated by increased ventricular hydroxyproline concentration (4.71 ± 0.12 mg/g vs 5.35 ± 0.17 mg/g in control and doxycycline groups, respectively). However, arterial pressure, aortic stiffness (pulse wave velocity), and left ventricular function were unaffected.
  
  
  CONCLUSIONS
  These findings suggest that moderate collagen accumulation does not by itself adversely affect cardiovascular function and that other changes in collagen properties (eg, formation of advanced glycation end-products) may be responsible for the adverse effects of myocardial fibrosis.
authors.affiliation: Hypertension Research Laboratory, Division of Research, Ochsner Clinic Foundation, New Orleans, LA.
authors.forename: Dinko
authors.initials: D
authors.lastname: Susic
authors.forename: Edward D
authors.initials: ED
authors.lastname: Frohlich