Dissociation between Cardiac Cyclic AMP and Myocardial Contractility Induced by Verapamil, Calcium and Magnesium Ions

Abstract

Isolated perfused rat hearts were used to study the effects of verapamil, excess Ca or Mg ions on changes in heart cyclic(c)AMP and myocardial force of contraction. Verapamil caused a dose-dependent decrease in force of contraction and a non-dose related reduction in cAMP. Perfusion of hearts with medium containing 5 mM Ca produced a significant rise in cAMP, but no change in contractile force. The depressant effects of verapamil on contractility and cAMP were reversed by 5 mM Ca; excess Ca in the perfusion fluid also containing verapamil prevented the myocardial depressant effects of verapamil. Acutely elevating the Mg concentration in the perfusion medium decreased the force of contraction and accentuated the negative inotropic effect of verapamil, but did not decrease cAMP or enhance the verapamil-induced reduction in cAMP.