(Hypertension. 2000;35:1203.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Altered Inotropic Responsiveness and Gene Expression of Hypertrophied Myocardium With Captopril
From the Cardiovascular Division, Boston Veterans Affairs Medical Center (W.W.B., O.H.L.B., N.S., W.S.C., C.H.C), Boston, Mass; the Department of Cardiology, Boston University School of Medicine, Boston, Mass; the Division of Kinesiology, University of Michigan (M.O.B.), Ann Arbor; Department of Medicine, University of Medicine and Dentistry New Jersey (A.M.), Newark, NJ; and the Department of Medicine (Cardiovascular Division), Beth Israel Hospital and Harvard Medical School (J.P.M.), Boston, Mass.
Correspondence to Wesley W. Brooks, DSc, Research Service (151), Boston VA Medical Center, 150 S Huntington Ave, Boston, MA 02130. E-mail conrad.chester{at}boston.va.gov
Abstract—Inotropic responsiveness
to ß-adrenergic stimulation is generally found to be impaired in left
ventricular (LV) hypertrophy and failure. To
investigate the mechanisms by which angiotensin-converting
enzyme inhibitor therapy may modulate inotropic
responsiveness with long-term pressure overload, we studied the effects
of captopril treatment on cardiac gene expression, LV muscle mechanical
contraction, and intracellular calcium (Ca2+) transients
from spontaneously hypertensive rats (SHR). LV papillary muscles from
untreated SHR, age-matched normotensive Wistar-Kyoto rats (WKY), and
SHR treated with captopril (CAPRx started at 12, 18, and 21
months of age) were studied. All animals were studied at 24 months of
age or when heart failure developed. In untreated SHR, 
-myosin heavy
chain (MHC) gene expression and protein were decreased,
the Ca2+ transient (with the bioluminescent indicator
aequorin) was prolonged, and abundance of
Na+/Ca2+ exchanger mRNA levels increased in
comparison to WKY. Active stress development at Lmax and
the maximum rate of stress development were depressed and contractile
duration prolonged in SHR relative to WKY. Isoproterenol administration
further decreased active stress in untreated SHR despite an increase in
intracellular Ca2+ levels. In CAPRx SHR,
-MHC gene expression and protein levels were
increased, the Ca2+ transient was not prolonged,
Na+/Ca2+ exchanger expression was
downregulated, and papillary muscle function demonstrated increased
active stress and maximum rate of stress development in response to
isoproterenol. The increased abundance of -MHC mRNA
in conjunction with an increase in V1 myosin isozyme
suggests that captopril affects transcriptional regulation of cardiac
gene expression. Restored LV inotropic responsiveness to ß-adrenergic
stimulation in CAPRx SHR appears to be coupled to
normalization of Na+/Ca2+ exchanger mRNA
expression, upregulation of V1 myosin isozyme levels, and
increased speed of contraction.
Key Words: hypertrophy, left ventricular • heart failure • calcium • receptors, adrenergic, beta
This article has been cited by other articles:
 |
|
 |
|
  O. H. Cingolani, X.-P. Yang, Y.-H. Liu, M. Villanueva, N.-E. Rhaleb, and O. A. Carretero Reduction of Cardiac Fibrosis Decreases Systolic Performance Without Affecting Diastolic Function in Hypertensive Rats Hypertension, May 1, 2004; 43(5): 1067 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R Sipido, P. G.A Volders, M. A Vos, and F. Verdonck Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc Res, March 1, 2002; 53(4): 782 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bartel, B. Hoch, D. Vetter, and E.-G. Krause Expression of Human Angiotensinogen-Renin in Rat: Effects on Transcription and Heart Function Hypertension, February 1, 2002; 39(2): 219 - 223. [Abstract] [Full Text] [PDF]
|
|