Caffeine and theophylline attenuate adenosine-induced vasodilation in humans

Abstract

In this study the local vasoactive effects of adenosine were explored in the human forearm. Adenosine (15 .mu.g/100 ml forearm/min) infused into the brachial artery (n = 6) increased forearm blood flow by 572% .+-. 140%, versus -0.5% .+-. 5.8% during placebo infusion (p < 0.01). Lower adenosine infusion rates (5 .mu.g/100 ml forearm/min, three times) induced forearm blood flow increments to 330% .+-. 94%, 339% .+-. 67% and 330% .+-. 79%, respectively (n = 8). These forearm blood flow responses were reduced (p = 0.02) during concomitant intra-arterial infusion of two doses of caffeine (30 and 90 .mu.g/100 ml forearm/min) to 150% .+-. 45% and 98% .+-. 28%, respectively. Theophylline (30 .mu.g/100 ml forearm/min; n = 6) also significantly attenuated the adenosine-induced increase in forearm blood flow. Enprofylline (30 .mu.g/100 ml forearm/min), a related xanthine with a low affinity to adenosine receptors in vitro, did not change the response to adenosine. Nonspecific vasodilation by sodium nitroprusside infusion (50 ng/100 ml forearm/min) was not inhibited by caffeine compared with placebo (forearm blood flow responses were 202% .+-. 21% versus 216% .+-. 40%; n = 6). This study demonstrated that caffeine and theophylline specifically reduce adenosine-induced vasodilation in humans, supporting the existence of functional human vascular adenosine receptors.