Swoap S J, Li C, Wess J, Parsons A D, Williams T D, Overton J M
Dept. of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300, USA.
Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1581-8. doi: 10.1152/ajpheart.01000.2007. Epub 2008 Feb 1.
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 T(a) is typically 21-23 degrees C, well below the thermoneutral zone ( approximately 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 T(a) to demonstrate the sensitivity of the mouse cardiovascular system to T(a). 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 (M(2)R(-/-)) mice], and 3) littermate controls. At a T(a) of 30 degrees 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 M(2)R(-/-) mice was significantly greater (416 +/- 7 beats/min), demonstrating that vagal tone predominates over HR control at this T(a). When these mice were calorically restricted to 70% of normal intake, HR fell equally in wild-type, beta-less, and M(2)R(-/-) mice (DeltaHR = 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 T(a) 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 M(2)R(-/-) 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.
一般认为,心脏交感神经张力主导小鼠心率(HR)的控制。然而,鉴于小鼠的心率对环境温度(T(a))有反应,且小鼠饲养环境的温度通常为21 - 23摄氏度,远低于该物种的热中性区(约30摄氏度),我们最近对这一观点提出了质疑。为了具体检验心脏交感神经张力是小鼠心率控制的主要调节因子这一假设,我们首先研究了对T(a)快速变化的代谢和心血管反应,以证明小鼠心血管系统对T(a)的敏感性。然后,我们测定了1)心脏交感神经张力缺乏的小鼠(“无β”小鼠)、2)心脏迷走神经张力缺乏的小鼠[毒蕈碱M(2)受体(M(2)R(-/-))小鼠]和3)同窝对照小鼠的心率。在30摄氏度的T(a)条件下,“无β”小鼠的心率与野生型小鼠相同(分别为351±11和363±10次/分钟)。然而,M(2)R(-/-)小鼠的心率显著更高(416±7次/分钟),表明在此T(a)条件下迷走神经张力在心率控制中占主导地位。当这些小鼠的热量摄入限制在正常摄入量的70%时,野生型、“无β”和M(2)R(-/-)小鼠的心率下降程度相同(分别为ΔHR = 73±9、76±3和73±7次/分钟),这表明内在心率的下降决定了热量限制小鼠的心动过缓。只有当T(a)相对较低,为23摄氏度时,“无β”小鼠的心率(442±14次/分钟)才与同窝对照小鼠(604±10次/分钟)和M(2)R(-/-)小鼠(602±5次/分钟)不同。这些实验确凿地证明,在没有冷应激的情况下,迷走神经张力的调节和内在心率的调节是小鼠心率控制的重要决定因素。