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It is known that adenosine decreases blood pressure (BP) level as well as blood pressure variability (BPV). However, there is little information about the effect of adenosine on BPV. With a computerized analytic system for BP and heart rate (HR) that could sample the data continuously in conscious, freely moving rats, we studied the effects of different agonists and antagonists of adenosine receptors on BPV in sinoaortic denervated (SAD) rats. It was found that both adenosine and 5′-N-cyclopropyl-carboxamidoadenosine (CPCA, a selective adenosine A2-receptor agonist) decreased BPV, whereas N6-cyclopentyladenosine (CPA, a selective adenosine A1-receptor agonist) had no significant effect on BPV. When the rats were pretreated with theophylline (the nonselective adenosinereceptor antagonist), the inhibitory effects of adenosine as well as CPCA on BPV were abolished. Furthermore, it was found that 8-(3-chlorostyryl)caffeine (CSC, a selective adenosine A2a-receptor antagonist), also could prevent such an effect on BPV of CPCA. By itself, however, neither theophylline nor CSC had any influence on BPV. These results suggest that the effect of adenosine on BPV is mediated by adenosine A2a-receptor.