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 fa ilure, we measured myocardial ouabain binding sites, Na-K-adenosinetri phosphatase (ATPase) activity, and ventricular muscle mechanical respo nses to acetylstrophanthidin in dogs with right-heart failure (RHF) pr oduced by tricuspid avulsion and pulmonary artery constriction. Sham-o perated dogs were studied as the control. RHF produced a significant d ecrease in ouabain binding sites in the right and left ventricular myo cardium, which was accompanied by a proportional decrease in Na-K-ATPa se activity. However, RHF and sham-operated dogs did not differ in sys temic hemodynamic or right ventricular trabeculate muscle isometric co ntractile responses to acetylstrophanthidin. To determine whether chro nic beta-adrenergic stimulation contributed to the development of Na-K -ATPase downregulation, we administered nadolol (40 mg/day) to a separ ate group of dogs during an early stage of RHF development. Nadolol ef fectively 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.