Laboratory of Physiological Regulation in Sleeping Mice (PRISM), Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
J Physiol. 2018 Feb 15;596(4):591-608. doi: 10.1113/JP275353. Epub 2018 Jan 19.
While values of arterial pressure during sleep are predictive of cardiovascular risk, the autonomic mechanisms underlying the cardiovascular effects of sleep remain poorly understood. Here, we assess the autonomic mechanisms of the cardiovascular effects of sleep in C57Bl/6J mice, taking advantage of a novel technique for continuous intraperitoneal infusion of autonomic blockers. Our results indicate that non-REM sleep decreases arterial pressure by decreasing sympathetic vasoconstriction, decreases heart rate by balancing parasympathetic activation and sympathetic withdrawal, and increases cardiac baroreflex sensitivity mainly by increasing fluctuations in parasympathetic activity. Our results also indicate that REM sleep increases arterial pressure by increasing sympathetic activity to the heart and blood vessels, and increases heart rate, at least in part, by increasing cardiac sympathetic activity. These results provide a framework for generating and testing hypotheses on cardiovascular derangements during sleep in mouse models and human patients.
The values of arterial pressure (AP) during sleep predict cardiovascular risk. Sleep exerts similar effects on cardiovascular control in human subjects and mice. We aimed to determine the underlying autonomic mechanisms in 12 C57Bl/6J mice with a novel technique of intraperitoneal infusion of autonomic blockers, while monitoring the electroencephalogram, electromyogram, AP and heart period (HP, i.e. 1/heart rate). In different sessions, we administered atropine methyl nitrate, atenolol and prazosin to block muscarinic cholinergic, β -adrenergic and α -adrenergic receptors, respectively, and compared each drug infusion with a matched vehicle infusion. The decrease in AP from wakefulness to non-rapid-eye-movement sleep (N) was abolished by prazosin but was not significantly affected by atropine and atenolol, which, however, blunted the accompanying increase in HP to a similar extent. On passing from N to rapid-eye-movement sleep (R), the increase in AP was significantly blunted by prazosin and atenolol, whereas the accompanying decrease in HP was blunted by atropine and abolished by atenolol. Cardiac baroreflex sensitivity (cBRS, sequence technique) was dramatically decreased by atropine and slightly increased by prazosin. These data indicate that in C57Bl/6J mice, N decreases mean AP by decreasing sympathetic vasoconstriction, increases HP by balancing parasympathetic activation and sympathetic withdrawal, and increases cBRS mainly by increasing fluctuations in parasympathetic activity. R increases mean AP by increasing sympathetic vasoconstriction and cardiac sympathetic activity, which also explains, at least in part, the concomitant decrease in HP. These data represent the first comprehensive assessment of the autonomic mechanisms of cardiovascular control during sleep in mice.
虽然睡眠期间的动脉血压值可预测心血管风险，但睡眠对心血管影响的自主神经机制仍知之甚少。在这里，我们利用一种新的连续腹腔内输注自主神经阻滞剂的技术，评估了 C57Bl/6J 小鼠睡眠对心血管影响的自主神经机制。我们的结果表明，非快速眼动 (N) 睡眠通过降低交感血管收缩来降低动脉血压，通过平衡副交感神经激活和交感神经抑制来降低心率，并通过增加副交感神经活动的波动来主要增加心脏压力反射敏感性。我们的结果还表明，快速眼动 (R) 睡眠通过增加心脏和血管的交感神经活动来增加动脉血压，并通过增加心脏交感神经活动至少部分增加心率。这些结果为在小鼠模型和人类患者中生成和测试睡眠期间心血管紊乱的假设提供了一个框架。
睡眠期间的动脉压 (AP) 值可预测心血管风险。睡眠对人类和小鼠的心血管控制具有相似的影响。我们旨在通过一种新的腹腔内输注自主神经阻滞剂的技术，在监测脑电图、肌电图、AP 和心率 (HP，即 1/心率) 的同时，确定 12 只 C57Bl/6J 小鼠的潜在自主神经机制。在不同的实验中，我们分别给予硝酸甲硫丁胺、阿替洛尔和普萘洛尔以阻断毒蕈碱型胆碱能、β -肾上腺素能和α -肾上腺素能受体，并将每种药物输注与匹配的载体输注进行比较。从觉醒到非快速眼动 (N) 睡眠时的 AP 下降被普萘洛尔消除，但阿托品类和阿替洛尔类对其无显著影响，但对伴随的 HP 增加的影响相似。从 N 到快速眼动 (R) 睡眠时，AP 的增加明显被普萘洛尔和阿替洛尔类阻断，而伴随的 HP 下降被阿托品类和阿替洛尔类阻断。心脏压力反射敏感性 (cBRS，序列技术) 被阿托品类和普萘洛尔类显著降低，而被普萘洛尔类略微增加。这些数据表明，在 C57Bl/6J 小鼠中，N 通过降低交感血管收缩来降低平均 AP，通过平衡副交感神经激活和交感神经抑制来增加 HP，并通过增加副交感神经活动的波动主要增加 cBRS。R 通过增加交感血管收缩和心脏交感神经活动来增加平均 AP，这也至少部分解释了伴随的 HP 下降。这些数据代表了对小鼠睡眠期间心血管控制自主神经机制的首次全面评估。
