Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality
Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality
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DOI：
10.1152/ajpheart.01000.2007
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发表时间：
2008-04-01
影响因子：
4.8
通讯作者：
Overton, J. M.
中科院分区：
文献类型：
--
作者：
Swoap, S. J.;Li, C.;Overton, J. M.
一般认为心脏交感神经张力在小鼠心率（HR）的控制中占主导地位。然而，我们最近对这一观点提出了质疑，因为小鼠的HR对环境温度（T-a）有反应，并且房屋Ta通常为21-23摄氏度，远低于该物种的热中性区（类似于30摄氏度）。为了具体测试心脏交感神经张力是小鼠HR控制的主要介质这一假设，我们首先检查了代谢和心血管对Ta快速变化的反应，以证明小鼠心血管系统对Ta的敏感性。然后，我们测定了1）心脏交感神经张力缺陷的小鼠（“β-少”小鼠），2）心脏迷走神经张力缺陷的小鼠[毒蕈碱M-2受体（M2 R-/-）小鼠]和3）同窝对照小鼠的HR。在Ta为30 ℃时，β-缺失小鼠的HR与野生型小鼠的HR相同（分别为351 +/-11次和363 +/-10次/分钟）。然而，M2 R（-/-）小鼠的HR显著更大（416 +/-7次/分钟），表明在该Ta下迷走神经张力优于HR控制。当这些小鼠的热量限制为正常摄入量的70%时，野生型、β-less和M2 R（-/-）小鼠的HR下降相等（Δ HR分别为73 +/- 9、76 +/- 3和73 +/- 7次/分钟），表明固有HR的下降控制热量限制小鼠的心动过缓。只有当Ta相对较冷时，即23 ℃时，β-less小鼠才表现出与同窝对照小鼠（604 +/-10次/分钟）和M2 R（-/-）小鼠（602 +/- 5次/分钟）不同的HR（442 +/- 14次/分钟）。这些实验最终证明，在没有冷应激的情况下，迷走神经张力的调节和固有频率的调制是小鼠HR控制的重要决定因素。
It is generally accepted that cardiac sympathetic tone dominates the control of heart rate (HR) in mice. However, we have recently challenged this notion given that HR in the mouse is responsive to ambient temperature (T-a) and that the housing Ta is typically 21-23 degrees C, well below the thermoneutral zone (similar to 30 degrees C) of this species. To specifically test the hypothesis that cardiac sympathetic tone is the primary mediator of HR control in the mouse, we first examined the metabolic and cardiovascular responses to rapid changes in Ta to demonstrate the sensitivity of the mouse cardiovascular system to Ta. We then determined HR in 1) mice deficient in cardiac sympathetic tone ("beta-less" mice), 2) mice deficient in cardiac vagal tone [muscarinic M-2 receptor (M2R-/-) mice], and 3) littermate controls. At a Ta of 30 C, the HR of beta-less mice was identical to that of wild-type mice (351 +/- 11 and 363 +/- 10 beats/min, respectively). However, the HR of M2R(-/-) mice was significantly greater (416 +/- 7 beats/min), demonstrating that vagal tone predominates over HR control at this Ta. When these mice were calorically restricted to 70% of normal intake, HR fell equally in wild-type, beta-less, and M2R(-/-) mice (Delta HR = 73 +/- 9, 76 +/- 3, and 73 +/- 7 beats/min, respectively), suggesting that the fall in intrinsic HR governs bradycardia of calorically restricted mice. Only when the Ta was relatively cool, at 23 degrees C, did beta-less mice exhibit a HR (442 +/- 14 beats/min) that was different from that of littermate controls (604 +/- 10 beats/min) and M2R(-/-) mice (602 +/- 5 beats/min). These experiments conclusively demonstrate that in the absence of cold stress, regulation of vagal tone and modulation of intrinsic rate are important determinants of HR control in the mouse.