title: Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice.
abstract: 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% O(2) and 5.7% O(2), 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 microg/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 microA, 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.
authors: Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, 4000 Central Florida Parkway, Orlando, FL 32816, USA.
authors: Min
authors: M
authors: Lin
authors: Rugao
authors: R
authors: Liu
authors: David
authors: D
authors: Gozal
authors: William B
authors: WB
authors: Wead
authors: Mark W
authors: MW
authors: Chapleau
authors: Robert
authors: R
authors: Wurster
authors: Zixi Jack
authors: ZJ
authors: Cheng
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000503:physiopathology; D000768:Anesthesia, General; D000777:Anesthetics; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000503:physiopathology; D004558:Electric Stimulation; D000431:Ethanol / Q000031:analogs & derivatives; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology*; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000777:Anesthetics; D014665:Vasodilator Agents; C062527:tribromoethanol; D009599:Nitroprusside; D010656:Phenylephrine; D000431:Ethanol