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1Department of Biology, Williams College, Williamstown, Massachusetts; 2Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; 3Department of Biomedical Sciences, Florida State University, Tallahassee, Florida; and 4Department of Biology, Emmanuel College, Boston, Massachusetts
Submitted 29 August 2007 ; accepted in final form 26 January 2008
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 (Ta) and that the housing Ta is typically 21–23°C, well below the thermoneutral zone (
30°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 ("β-less" mice), 2) mice deficient in cardiac vagal tone [muscarinic M2 receptor (M2R–/–) mice], and 3) littermate controls. At a Ta of 30°C, the HR of β-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, β-less, and M2R–/– mice (
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°C, did β-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.
telemetry; intrinsic heart rate; cold stress; caloric restriction; sympathetic nervous system
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