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A randomized, double-blind and placebo-eon-trolled study was performed in 10 normotensive male subjects to analyze a possible antagonism between caffeine and adenosine with respect to their effects on the cardiovascular system in humans. Caffeine alone. 250 mg intravenously (i.v.). increased blood pressure by 9/12 mm Hg. and resulted in a fall of heart rate (HR) of 3 beats/ min. Plasma epinephrine (E) rose by 1149? after caffeine. Adenosine alone, in an increasing dose of 0.04–0.16 mg/kg/min, induced an increase in systolic blood pressure (SBP) (17 mm Hg). and HR (33 beats/min). a moderate fall in diastolic blood pressure (DBP) (-4 mm Hg). and no change of mean arterial pressure (MAP). At the highest adenosine infusion rate, forearm blood How. Skin temperature (ST), and transcutaneous oxygen tension were lowered, whereas plasma (nor)epinephrine was increased 227.2 and 215.9%, respectively. Adenosine infusion after caffeine induced comparable effects, but the fractional adenosine-induced changes of SBP. HR, plasma catecholamines, plasma renin activity (PRA), and aldosterone all were significantly reduced by previous administration of caffeine. Our results indicate an antagonism between caffeine and adenosine in humans, which may support the suggestion that some circulatory effects of caffeine are caused by an interaction with endogenous adenosine.