Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart failure: prevention by nadolol.
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 beta-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.
Fan
T H
TH
Department of Medicine, University of Rochester Medical Center, New York 14642.
Frantz
R P
RP
Elam
H
H
Sakamoto
S
S
Imai
N
N
Liang
C S
CS
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009248:Nadolol / Q000494:pharmacology*; D010042:Ouabain / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D016278:Ventricular Function, Right / Q000187:drug effects
D009248:Nadolol; D010042:Ouabain; D013327:Strophanthidin; D000254:Sodium-Potassium-Exchanging ATPase; C004681:acetylstrophanthidin