TY - JOUR
T1 - Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart failure
T2 - Prevention by nadolol
AU - Fan, T. H.M.
AU - Frantz, R. P.
AU - Elam, H.
AU - Sakamoto, S.
AU - Imai, N.
AU - Liang, C. S.
PY - 1993
Y1 - 1993
N2 - To study the changes in myocardial digitalis binding sites in heart failure, we measured myocardial ouabain binding sites, Na-K- adenosinetriphosphatase (ATPase) activity, and ventricular muscle mechanical responses to acetylstrophanthidin in dogs with right-heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. Sham- operated dogs were studied as the control. RHF produced a significant decrease in ouabain binding sites in the right and left ventricular myocardium, which was accompanied by a proportional decrease in Na-K-ATPase activity. However, RHF and sham-operated dogs did not differ in systemic hemodynamic or right ventricular trabeculate muscle isometric contractile responses to acetylstrophanthidin. To determine whether chronic β-adrenergic stimulation contributed to the development of Na-K-ATPase downregulation, we administered nadolol (40 mg/day) to a separate group of dogs during an early stage of RHF development. Nadolol effectively prevented the reduction of myocardial ouabain binding sites that occurred in RHF. Thus we conclude that myocardial ouabain binding sites and Na-K-ATPase activity are reduced in dogs with experimental heart failure and that these changes probably occur as a result of the attendant heightened sympathetic activity.
AB - To study the changes in myocardial digitalis binding sites in heart failure, we measured myocardial ouabain binding sites, Na-K- adenosinetriphosphatase (ATPase) activity, and ventricular muscle mechanical responses to acetylstrophanthidin in dogs with right-heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. Sham- operated dogs were studied as the control. RHF produced a significant decrease in ouabain binding sites in the right and left ventricular myocardium, which was accompanied by a proportional decrease in Na-K-ATPase activity. However, RHF and sham-operated dogs did not differ in systemic hemodynamic or right ventricular trabeculate muscle isometric contractile responses to acetylstrophanthidin. To determine whether chronic β-adrenergic stimulation contributed to the development of Na-K-ATPase downregulation, we administered nadolol (40 mg/day) to a separate group of dogs during an early stage of RHF development. Nadolol effectively prevented the reduction of myocardial ouabain binding sites that occurred in RHF. Thus we conclude that myocardial ouabain binding sites and Na-K-ATPase activity are reduced in dogs with experimental heart failure and that these changes probably occur as a result of the attendant heightened sympathetic activity.
KW - congestive heart failure
KW - nadolol
KW - norepinephrine
KW - ouabain binding sites
KW - sodium-potassium pump
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U2 - 10.1152/ajpheart.1993.265.6.h2086
DO - 10.1152/ajpheart.1993.265.6.h2086
M3 - Article
C2 - 8285248
AN - SCOPUS:0027763140
SN - 0002-9513
VL - 265
SP - H2086-H2093
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 34-6
ER -