title: Effects of chronic angiotensin-converting enzyme inhibition on left ventricular and myocyte structure and function during recovery from chronic rapid pacing.
abstract: LV and myocyte function and angiotensin converting enzyme (ACE) activity with ACE inhibitor (ACEI) treatment were examined in four groups of dogs (n = 6 each): (1) control; (2) with 4 weeks of recovery from chronic rapid pacing (REC: 216 beats/min), (3) ACEI for the first 14 days of REC (ACEI--14), and (4) ACEI for 28 days of REC (ACEI--28). Three additional control dogs were administered ACEI for 28 days. LV mass increased with REC compared to control (146 +/- 6 v 92 +/- 3 g, P < 0.05), was unaffected with ACEI--14, and was decreased with ACEI--28 compared to REC (111 +/- 8 g, P < 0.05). Myocyte function was decreased in REC compared to controls (43 +/- 3 v 63 +/- 3 microns/s, P < 0.05) and was similarly reduced with ACEI--14. However, with ACEI--28, myocyte shortening velocity was increased compared to REC (56 +/- 1 microns/s, P < 0.05). Myocyte beta-adrenergic response was decreased with REC and ACEI--14 compared to controls (53 +/- 9 and 57 +/- 14, respectively v 127 +/- 14 microns/s, P < 0.05). ACEI--28 resulted in a normalization of myocyte beta-adrenergic responsiveness (108 +/- 3 microns/s). LV myocardial ACE activity increased in REC compared to control (5.82 +/- 0.21 v 3.51 +/- 0.15 nmol/mg/min, P < 0.05). With ACEI--14 or ACEI--28, myocardial ACE activity was decreased compared to REC (4.16 +/- 0.06 and 4.08 +/- 0.23 nmol/mg/min; P < 0.05). In control dogs administered ACEI, there were no differences in any of these parameters compared to controls. The unique findings in this study were: (1) effects of ACEI treatment in this model of LV hypertrophy were time dependent with respect to LV mass and LV and myocyte function; and (2) the effect of ACEI treatment on the degree of LV hypertrophy appears to not be solely due modulation of myocardial ACE activity.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Melton
authors.forename: H H
authors.initials: HH
authors.lastname: Holzgrefe
authors.forename: J D
authors.initials: JD
authors.lastname: Walker
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: S R
authors.initials: SR
authors.lastname: Arthur
authors.forename: M J
authors.initials: MJ
authors.lastname: Antonaccio
authors.forename: W H
authors.initials: WH
authors.lastname: Koster
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D005260:Female; D006339:Heart Rate; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000473:pathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000318:Adrenergic beta-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D007545:Isoproterenol