Correlation of cyclic AMP and cyclic GMP levels with changes in contractile force of dog ventricular myocardium during cholinergic antagonism of positive inotropic actions of histamine, glucagon, theophylline and papaverine.

Abstract

On the dog isolated right ventricular muscle, experiments were performed to elucidate the characteristics of the cholinergic antagonism against the positive inotropic action (PIA) induced via different subcellular mechanisms. The relationship between cyclic[c]AMP and cGMP levels, and contractile force during cholinergic antagonism was assessed. Carbachol (10 .mu.M) decreased only slightly the tension developed, but inhibited prominently the PIA of isoprenaline, histamine, glucagon, theophylline and papaverine. The action of dibutyryl cAMP was inhibited less than PIA of other agents. Carbachol did not affect the PIA of Ca and g-strophanthin. The antagonism by carbachol of PIA of isoprenaline, histamine, glucagon, theophylline and papaverine was accompanied by a reduction of the intracellular cAMP level elevated previously by these agents, and by an elevation of the intracellular cGMP level. A good correlation was found between changes in the tension developed, and cAMP and cGMP levels during the cholinergic antagonism of PIA induced by the agents in the dog ventricular myocardium.