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The involvement of endothelial adenosine A2receptor-cAMP system in A2receptor-mediated vasodilation in human aortic endothelial cells (HAEC) was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of both A2aand A2breceptors mRNA in HAEC. In HAEC, YT-146 (selective A2receptor-agonist) produced a dose dependent increase of cAMP production. This increase was inhibited by theophylline. YT-146 also showed a vasodilatory action in isolated rat aorta. The removal of endothelium significantly attenuated this vasodilatory effect. Our results provide the first evidence for the expression of both subtypes of the A2aand A2breceptors which regulate cAMP production in human endothelial cells. The present results also suggest that A2receptor-cAMP system was involved in the endothelium-dependent vasodilatory actions and may play important roles in regulating vascular functions of HAEC.