Attenuation of heart rate control and neural degeneration in nucleus ambiguus following chronic intermittent hypoxia in young adult fischer 344 rats

    Authors

    B. Yan; G. K. Soukhova-O'Hare; L. Li; Y. Lin; D. Gozal; W. B. Wead; R. D. Wurstere;Z. J. Cheng

    Comments

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    Abbreviated Journal Title

    Neuroscience

    Keywords

    baroreflex; nucleus ambiguus; parasympathetic; cardiac ganglia; heart; intermittent hypoxia; SPATIAL-LEARNING DEFICITS; VAGAL PREGANGLIONIC NEURONS; VENTRAL; RESPIRATORY GROUP; OBSTRUCTIVE SLEEP-APNEA; LATERAL TEGMENTAL FIELD; CARDIAC GANGLIA; SUBNUCLEAR ORGANIZATION; BAROREFLEX SENSITIVITY; BARORECEPTOR REFLEX; OXIDATIVE STRESS; Neurosciences

    Abstract

    Chronic intermittent hypoxia (CIH) attenuates baro-reflex control of heart rate (HR). In this study, we assessed whether CIH exposure reduced nucleus ambiguus (NA) control of HR and induced neural degeneration in the NA. Fischer 344 (age: 3-4 months) rats were exposed to either room air (RA: normoxia) or intermittent hypoxia for 35-50 days. At the end of these exposures, animals were anesthetized with pentobarbital. HR responses to arterial blood pressure (AP) changes induced by phenylephrine (PE) and sodium nitroprusside (SNP) were measured. In another set of rats, HR and AP responses to L-glutamate (L-Glu) microinjections (10 mM, 20 nl) into the left NA and electrical stimulation of the left cervical vagus nerve at 1-30 Hz (0.5 mA, 1 ms) for 20 s were measured. Brainstem slices at the level of -800, -400, 0, +400, +800 mu m relative to the obex were processed in additional rats using Nissl staining. The NA was identified by retrogradely labeling vagal motoneurons using the tracer tetra-methylrhodamine dextran (TMR-D) which was injected into the ipsilateral nodose ganglion. We found that CIH significantly 1) reduced the baro-reflex control of HR (slope RA: -1.2 +/- 0.2 bpm/ mmHg; CIH -0.5 +/- 0.1 bpm/mmHg; P < 0.05); 2) attenuated the HR responses to L-Glu injections into the NA [HR: -280 +/- 15 (RA) vs. -235 +/- 16 (CIH) beats/min; P < 0.05]; 3) augmented the HR responses to electrical stimulation of the vagus (P < 0.05); 4) induced a significant cellular loss in the NA region (P < 0.05). Thus, CIH induces a cell loss in the NA region which may contribute to attenuation of baroreflex sensitivity and NA control of HR following CIH. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

    Journal Title

    Neuroscience

    Volume

    153

    Issue/Number

    3

    Publication Date

    1-1-2008

    Document Type

    Article

    Language

    English

    First Page

    709

    Last Page

    720

    WOS Identifier

    WOS:000256042400016

    ISSN

    0306-4522

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