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

2005年，我们发现腺苷A2a受体敲除小鼠在REM睡眠期间动脉压（AP）和心率（HR）升高，而野生型小鼠则没有。在本研究中，我们试图阐明AP和HR升高与腺苷受体相关的机制。我们使用腺苷受体拮抗剂观察到的结果如下：1)非选择性腺苷受体拮抗剂咖啡因不影响小鼠快速眼动睡眠时AP和HR的变化。2)腺苷Al受体拮抗剂CPT和腺苷A2a受体拮抗剂SCH58261均不影响小鼠快速眼动睡眠时AP和HR的变化。3) CPT诱导小鼠焦虑，而SCH58261没有。由于在上述药理学研究中没有发现明显的结果，我们将重点从药理学研究转向呼吸功能的观察。我们同时监测小鼠的呼吸和AP，发现REM睡眠期间呼吸暂停后AP激增。碳酸酐酶抑制剂乙酰唑胺增加通气频率，抑制REM睡眠期间AP上升。这些数据提示快速眼动睡眠期间AP的增加可能与呼吸功能的改变有关。有报道称腺苷受体也参与呼吸调节，可能是腺苷A2a受体敲除小鼠的呼吸功能发生改变，从而改变REM睡眠时的AP和HR。

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.