title: Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs.
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.
authors.affiliation: Department of Medicine, Birmingham Veterans Affairs Medical Center, Alabama, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Dell'italia
authors.forename: E
authors.initials: E
authors.lastname: Balcells
authors.forename: Q C
authors.initials: QC
authors.lastname: Meng
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.forename: D
authors.initials: D
authors.lastname: Schultz
authors.forename: S P
authors.initials: SP
authors.lastname: Bishop
authors.forename: N
authors.initials: N
authors.lastname: Machida
authors.forename: I M
authors.initials: IM
authors.lastname: Straeter-Knowlen
authors.forename: G H
authors.initials: GH
authors.lastname: Hankes
authors.forename: R
authors.initials: R
authors.lastname: Dillon
authors.forename: R E
authors.initials: RE
authors.lastname: Cartee
authors.forename: S
authors.initials: S
authors.lastname: Oparil
mesh_terms: 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
chemical_list: 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