Adenosine as inhibitor of myocardial effects of catecholamines

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Abstract
Summary Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dosedependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4×10−11 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 (3×10−7 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.