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Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality

1 Department of Biology, Williams College, Williamstown, Massachusetts; 2 Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; 3 Department of Biomedical Sciences, Florida State University, Tallahassee, Florida; and 4 Department of...

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Published in:American journal of physiology. Heart and circulatory physiology 2008-04, Vol.294 (4), p.H1581-H1588
Main Authors: Swoap, S. J, Li, C, Wess, J, Parsons, A. D, Williams, T. D, Overton, J. M
Format: Article
Language:English
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Summary:1 Department of Biology, Williams College, Williamstown, Massachusetts; 2 Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; 3 Department of Biomedical Sciences, Florida State University, Tallahassee, Florida; and 4 Department 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 (T a ) and that the housing T a 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 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 ("β-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°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 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, β-less, and M 2 R –/– 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 T a 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 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. telemetry; intrinsic heart rate; cold stress; caloric restriction; sympathetic nervous system Address for reprint requests and other correspondence: J. Michael Overton, Dept. of Biomedical Sciences, 3350-E College of Medicine, Florida State Univ., Tallahassee, FL 32306-4300 (e-mail: mike.overton{at}fsu.e
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.01000.2007