Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs.
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.
Dell'italia
L J
LJ
Department of Medicine, Birmingham Veterans Affairs Medical Center, Alabama, USA.
Balcells
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Meng
Q C
QC
Su
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Schultz
D
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Bishop
S P
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Machida
N
N
Straeter-Knowlen
I M
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Hankes
G H
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Dillon
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Cartee
R E
RE
Oparil
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D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D002469:Cell Separation; D053818:Chymases; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D006352:Heart Ventricles; D006439:Hemodynamics; D006940:Hyperemia / Q000150:complications*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics; D012697:Serine Endopeptidases / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases