The role of adenosine in insulin-induced vasodilation

It was previously shown that systemic hyperinsulinemia induces vasodilation in human skeletal muscle. The mechanism mediating this vasodilation is not yet completely clarified. Based on data from animal experiments, we hypoth esized that stimulation of the adenosine receptor is involved in insulin-in duced vasodilation. To test this hypothesis, a 105-min hyperinsulinemic eug lycemic clamp was performed in three groups of eight healthy volunteers. In group I, placebo was infused into the left brachial artery (experimental f orearm). In the second and third group, respectively, draflazine (an adenos ine-uptake blocker) and theophylline (an adenosine-receptor antagonist) wer e administered by intrabrachial infusion. Forearm blood flow (FBF) was meas ured by venous-occlusion plethysmography, both at the experimental and the control fore-arms. The percentage decrease in flow ratio (FBF experimental arm/control arm) in the draflazine group was significantly less pronounced than that in the placebo group, whereas the percentage decrease in flow rat io was larger in the theophylline group. These results demonstrate that the insulin-induced increase in blood flow in the experimental arm was more pr onounced at the site of adenosine-uptake blockade by draflazine, whereas th is was reduced during adenosine-receptor antagonism by theophylline. Our ob servations are compatible with the hypothesis that insulin-induced vasodila tion is mediated by the release of adenosine.