THE ACTION OF IMIDAZOLE ON THE EFFECTS OF METHYLXANTHINES AND CATECHOLAMINES ON CARDIAC CONTRACTION AND PHOSPHORYLASE ACTIVITY

¹ Department of Pharmacology, University of Graz, Graz, Austria

The effects of imidazole on the inotropic and phosphorylase-stimulating actions of catecholamines and methylxanthines were studied in the isolated perfused guinea-pig heart. Imidazole significantly reduced the effects of theophylline and caffeine on heart phosphorylase and cardiac contractility, but did not alter either response to isoproterenol unless the amine was given in very small amounts. Norepinephrine enhanced the imidazole-induced blockade of the cardiotonic and enzymestimulating actions of theophylline. The results support the hypothesis that the action of catecholamines on the heart is related to their ability to increase the rate of adenosine-3',5'-phosphate (3',5'-AMP) formation and that the cardiac effects of methylxanthines are due to inhibition of the phosphodiesterase responsible for the hydrolysis of 3',5'-AMP.