Effects of various drugs on myocardial cyclic AMP.

Effects of norepinephrine, J3-adrenergic blocking agents, theophylline ethylenediamine (TEDA) and digoxin on myocardial cyclic AMP concentration and those of various vasodilators both on myocardial cyclic AMP in vivo and phosphodiesterase (PDE) activity in vitro were investigated by radioimmunoassay of cyclic AMP. The mean concentration of myocardial cyclic AMP was 0.318 p mole/mg in the left ventricle, 0.204 p mole/mg in the right ventricle, 0.131 p mole/mg in the left atrium and 0.094 p mole/mg in the right atrium. Norepinephrine increased the concentration of cyclic AMP in the left ventricle significantly, while digoxin increased it only slightly, J3-adrenergic blocking agents did not decrease it, and TEDA elevated the concentration of left ventricular cyclic AMP. The myocardial cyclic AMP concentration of the ventricular fibrillation group increased significantly as compared with the non-ventricular fibrillation group. Dipyridamole, TEDA and prenylamine were determined as competitive inhibitors of purified heart PDE in vitro. These findings suggest that norepinephrine, TEDA and propranolol affect myocardial contractility through the cyclic AMP-PDE system and that TEDA, dipyridamole and prenylamine cause increase of myocardial cyclic AMP through the inhibition of PDE. It also suggests that there is a relationship between high myocardial concentration of cyclic AMP and ventricular fibrillation induced by PDE.