EFFECTS OF PAPAVERINE AND ITS INTERACTION WITH ISOPRENALINE AND CARBACHOL ON THE CONTRACTILE-FORCE AND CYCLIC NUCLEOTIDE LEVELS OF THE CANINE VENTRICULAR MYOCARDIUM

In the isolated ventricular myocardium of the dog, the effects of papaverine on the contractile force and on the cyclic nucleotide levels were studied. The interaction between papaverine and the adrenergic .beta.- or cholinergic stimulation was studied. Papaverine (3 .times. 10-5 M) induced a positive inotropic action and increased the cyclic [c]AMP level in the majority of preparations. Ventricular muscles isolated from certain dogs showed only a negative inotropic response to papaverine. A significant correlation was found between the tension developed and the cAMP level after the administration of papaverine. The cGMP level was not changed or decreased by papaverine. The positive inotropic action of papaverine and elevation of the cAMP level in response to papaverine were not inhibited by a .beta.-adrenoceptor blocking drug, pindolol (3 .times. 10-8 M), these effects are not caused by catecholamine release. In muscles in which papaverine failed to cause the positive inotropic action contractile and cAMP responses to isoprenaline were significantly enhanced by papaverine. Carbachol (3 .times. 10-6 M) diminished the positive inotropic actions of isoprenaline and papaverine, abolished the accumulation of cAMP produced by these agents and increased significantly the cGMP level. The elevation of cGMP level by carbachol in the presence of papaverine was especially marked and amounted to 4-fold the corresponding control value. Apparently papaverine inhibits the break down of the intracellular cAMP and GMP in the intact myocardial cells and may interact functionally with the autonomic nervous system.