Adenosine as inhibitor of myocardial effects of catecholamines

Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4 X 10(-11) moles). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) occurred at 10(-5) M. Coronary dilation induced by papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10(-5) M) effectively inhibited the isoproterenol (10(-7)M) induced initial rise in myocardial levels of cyclic 3'5'-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development. Upon infusion of isoproterenol (3 X 10(-7)M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10(-8) M to about 10(-6) M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines.