A ROLE FOR ADENOSINE IN CORONARY VASOREGULATION IN MAN - EFFECTS OF THEOPHYLLINE AND ENPROFYLLINE

Adenosine has been suggested to have a role in regulation of the tone of the cardiac resistance vessels. To elucidate the coronary vasoregul atory role of endogenous adenosine in man, we studied the effects of a denosine receptor antagonism by theophylline on coronary blood flow at rest and during light exercise. However, theophylline may also exert pharmacological effects not related to adenosine antagonism. To clarif y the contribution of endogenous adenosine in coronary hyperaemia, the effect of theophylline was compared to that of enprofylline, a xanthi ne which exerts similar pharmacological effects as theophylline while lacking antagonistic action at adenosine receptors. Twenty healthy sub jects (10 males) aged 22-39 years were examined. Coronary sinus (CS) b lood flow and blood oxygen content were determined at rest and during supine bicycle exercise, at a load of 50 watts, for 10 min. Thereafter , stepwise infusion of adenosine (30 to 60 mu g/kg/min into the subcla vian vein) was performed. Theophylline or enprofylline treatment was i nstituted randomly and double-blind (10 in each group), and the proced ures (i.e. determinations at rest, during exercise and during infusion of adenosine) were repeated. In all 20 subjects, basal CS flow was 70 +/- 6 ml/min and the cardiac oxygen extraction ((A-CS)O2D) was 123 +/ - 3 ml/l. During exercise, CS flow and (A-CS)O2D increased to 135 +/- 17 ml/min and 132 +/- 3 ml/l, respectively. Adenosine increased CS now dose dependently to 161 +/- 27 ml/min, while (A-CS)O2D decreased to 6 6 +/- 7 ml/l. The vasodilatory effect of adenosine was readily counter acted by theophylline, the increase in CS now being 33% vs. 133% in th e control situation. Enprofylline, on the other hand, enhanced the res ponse to exogenous adenosine. Theophylline, at a dose lacking effect o n heart rate and blood pressure, decreased CS now at rest by 14% (P < 0.05) and during exercise by 18% (P < 0.05). ((A-CS)O2D increased by 1 4% at rest and during exercise (P < 0.001). Enprofylline, on the other hand, was without effect. The differences in responses between theoph ylline and enprofylline with respect to coronary flow and oxygen extra ction were significant both at rest and during exercise. It is conclud ed that theophylline increases coronary vascular resistance, while enp rofylline, lacking adenosine antagonistic properties, was without such effect. This indicates a physiological role of adenosine in regulatio n of coronary flow.