Why do arterial pressure and heart rate increase during REM sleep in adenosine A2a knockout mice?

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In 2005, we have found that adenosine A2a receptor knockout mice show the increase of arterial pressure (AP) and heart rate (HR) during REM sleep, while wild-type mice do not. In this study, we tried to clarify the mechanism of the increase of AP and HR related with the adenosine receptors. Results we have observed by using the antagonist for the adenosine receptors are as follows;1) Caffeine, non-selective antagonist for adenosine receptor, did not affect the alteration of AP and HR during REM sleep in mice.2) Neither CPT, adenosine Al receptor antagonist, nor SCH58261, adenosine A2a receptor antagonist affected the alteration of AP and HR during REM sleep in mice.3) CPT induced anxiety of mice, while SCH58261 did not.Because we could not find the significant results in the above-mentioned pharmacological study, we have changed our focus from the pharmacological study to the observation of respiratory function. We monitored the respiration and AP simultaneously in the mice, and we have found that apnea during REM sleep is followed by the surge of AP. Acetazolamide, carbonic anhydrase inhibitor, increased the frequency of ventilation and suppressed the rise of AP during REM sleep. These data indicate that the increase of AP during REM sleep may be linked with the change of respiratory function. As it has been reported that adenosine receptors are also involved in the regulation of respiration, it is possible that, in adenosine A2a receptor knockout mice, respiratory function is altered and then AP and HR during REM sleep are modified.