The effect of beta adrenergic antagonists on cardiac contractions, myofibrillar ATPase activity, high-energy phosphate stores and lipid-facilitated transfort of calciumiones.

Abstract

The actions of a series of beta adrenergie receptor blocking compounds on the tension developed by dog and rabbit papillary muscles during isometric contraction were determined and compared with the effect of these same drugs on the activity of the myofibrillar adenosine triphosphatase (ATPase) enzyme and on lipid-facilitated transport of calcium ions. In addition, dogs on right-sided cardiac bypass were used to determine whether a change in ATP and creatine phosphate in heart muscle is associated with the negative inotropic effect of dl -propranolol. The other beta antagonists used were LB 46, ICI 50,172 and KO 592. The effect of these beta antagonists on myocardial contractility was not paralleled by their effect on the activity of the myofibrillar ATP enzyme; their inotropic action was, however, paralleled by their effect on the lipid-facilitated transport of Ca ++ across an aqueous lipid-solvent interface. The negative inotropic effect of dl -propranolol was not accompanied by any significant change in the concentrations of either ATP or creatine phosphate in heart muscle. It is concluded that the effects of these drugs on lipid-facilitated transport of Ca ++ determine their effect on cardiac contractility.