Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs.

Academic Article

Abstract

  • We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy prevents volume-overload hypertrophy in dogs with chronic mitral regurgitation (MR). Seven adult mongrel dogs receiving ramipril (R; 10 mg orally, twice/day) for 4 mo were compared with 11 dogs receiving no R (N) for 4 mo after induction of MR. Cine-magnetic resonance imaging demonstrated that left ventricular (LV) mass increased in the R-MR dogs [80 +/- 4 (SE) to 108 +/- 7 g, P < 0.01] and in the N-MR dogs (92 +/- 7 to 112 +/- 8 g, P < 0.001). LV myocyte cell length was greater in the R-MR and N-MR dogs (203 +/- 6 and 177 +/- 10 microns, respectively) than in normal (144 +/- 4 microns, P < 0.05) dogs. There was significant loss of the collagen weave pattern by scanning electron microscopy in both R-MR and N-MR dogs. LV ACE and chymase activities were significantly elevated in R-MR and N-MR compared with normal dogs. LV angiotensin II (ANG II) levels in the R-MR dogs (28 +/- 12 pg/g) were reduced to levels seen in normal dogs (28 +/- 4 pg/g) compared with N-MR dogs (72 +/- 11 pg/g, P < 0.05). Steady-state AT1-receptor mRNA levels decreased 66% in N-MR compared with normal dogs (P < 0.001) and increased 1.5-fold in R-MR compared with normal dogs (P < 0.01). Thus upregulation of the AT1 receptor in the R-MR hearts may provide a mechanism by which normal intracardiac ANG II levels could continue to mediate LV hypertrophy. However, the mechanism of dissolution collagen weave in both N-MR and R-MR hearts may be related to the stretch of volume overload.
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    Published In

    Keywords

  • Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Animals, Cardiomegaly, Cell Separation, Chymases, Collagen, Dogs, Heart Ventricles, Hemodynamics, Hyperemia, Myocardium, Peptidyl-Dipeptidase A, RNA, Messenger, Receptors, Angiotensin, Serine Endopeptidases
  • Digital Object Identifier (doi)

    Author List

  • Dell'italia LJ; Balcells E; Meng QC; Su X; Schultz D; Bishop SP; Machida N; Straeter-Knowlen IM; Hankes GH; Dillon R
  • Start Page

  • H961
  • End Page

  • H970
  • Volume

  • 273
  • Issue

  • 2 Pt 2