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Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice

¹Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, Florida; ²Department of Anatomy and Cell Biology, University of North Dakota School of Medicine, Grand Forks, North Dakota; ³Kosair Children's Hospital Research Institute, Department of Pediatrics, ⁴Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky; ⁵Department of Internal Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa; ⁶Department of Physiology, Loyola University, Stritch School of Medicine, Maywood, Illinois

Submitted 14 October 2006 ; accepted in final form 21 March 2007

Chronic intermittent hypoxia (CIH) leads to increased sympathetic nerve activity and arterial hypertension. In this study, we tested the hypothesis that CIH impairs baroreflex (BR) control of heart rate (HR) in mice, and that decreased cardiac chronotropic responsiveness to vagal efferent activity contributes to such impairment. C57BL/6J mice were exposed to either room air (RA) or CIH (6-min alternations of 21% O₂ and 5.7% O₂, 12 h/day) for 90 days. After the treatment period, mice were anesthetized (Avertin) and arterial blood pressure (ABP) was measured from the femoral artery. Mean ABP (MABP) was significantly increased in mice exposed to CIH (98.7 ± 2.5 vs. RA: 78.9 ± 1.4 mmHg, P < 0.001). CIH increased HR significantly (584.7 ± 8.9 beats/min; RA: 518.2 ± 17.9 beats/min, P < 0.05). Sustained infusion of phenylephrine (PE) at different doses (0.1–0.4 µg/min) significantly increased MABP in both CIH and RA mice, but the ABP-mediated decreases in HR were significantly attenuated in mice exposed to CIH (P < 0.001). In contrast, decreases in HR in response to electrical stimulation of the left vagus nerve (30 µA, 2-ms pulses) were significantly enhanced in mice exposed to CIH compared with RA mice at low frequencies. We conclude that CIH elicits a sustained impairment of baroreflex control of HR in mice. The blunted BR-mediated bradycardia occurs despite enhanced cardiac chronotropic responsiveness to vagal efferent stimulation. This suggests that an afferent and/or a central defect is responsible for the baroreflex impairment following CIH.

nucleus ambiguus; obstructive sleep apnea; cardiac ganglia

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				H. Gu, M. Lin, J. Liu, D. Gozal, K. E. Scrogin, R. Wurster, M. W. Chapleau, X. Ma, and Z. Cheng Selective impairment of central mediation of baroreflex in anesthetized young adult Fischer 344 rats after chronic intermittent hypoxia Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2809 - H2818. [Abstract] [Full Text] [PDF]