Cardiovascular effects of two xanthines and the relation to adenosine antagonism

We hypothesize that the hemodynamic effects of xanthine derivatives depend on their ability to antagonize the vasodilating effects of endogenous adenosine. In a randomized, double-blind, and placebo-controlled study of 10 normotensive volunteers caffeine, a xanthine with in vitro adenosine antagonistic properties, increased mean arterial pressure by 5.6 +/- 0.9 mm Hg and lowered heart rate by 5.3 +/- 1.1 beats/min. After administration of enprofylline, a xanthine without adenosine antagonism, forearm vascular resistance decreased by 5.6 +/- 3.4 IU, heart rate increased by 10.6 +/- 2.6 beats/min, and plasma adrenaline, plasma noradrenaline, and renin activity increased by 178 +/- 86%, 14 +/- 8%, and 36 +/- 13%, respectively. Adenosine infusion alone induced a dose-related increase in pulse pressure and heart rate, and it increased plasma adrenaline and noradrenaline by 186 +/- 77% and 132 +/- 55%, respectively. This response to adenosine was reduced by pretreatment with caffeine but not enprofyline. Thus opposite circulatory responses to caffeine and enprofylline occurred, with signs of vasoconstriction and vasodilation, respectively. In addition, caffeine, but not enprofylline, reduced the cardiovascular response to exogenous adenosine.