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

Yan, Bin; Soukhova-O'Hare, Galia K.; Li, L.; Lin, Ying; Gozal, David; Wead, William B.; Wurster, Robert D.; Cheng, Zixi

doi:10.1016/j.neuroscience.2008.01.066

Cited by 46 publications

(47 citation statements)

References 43 publications

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“…In contrast to our results in juvenile conscious, freely moving rats, studies in anesthetized mice [34] or young adult Fischer 344 rats [35,36] subjected to CIH documented that hypertension with CIH is associated with impairment of the cardiac baroreflex. In addition to differences in animal strain and the use of anaesthesia, these studies evaluated the baroreflex after 1 to 3 months of CIH [34][35][36], whereas the time of exposure in our studies was 10 days [9•].…”

Section: Chemoreflex and Baroreflex After Chronic Intermittent Hypoxiacontrasting

confidence: 99%

“…In addition to differences in animal strain and the use of anaesthesia, these studies evaluated the baroreflex after 1 to 3 months of CIH [34][35][36], whereas the time of exposure in our studies was 10 days [9•]. Possibly there is a time lag between the development of hypertension and cardiac baroreflex dysfunction.…”

Section: Chemoreflex and Baroreflex After Chronic Intermittent Hypoxiamentioning

confidence: 99%

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Coupling Between Respiratory and Sympathetic Activities as a Novel Mechanism Underpinning Neurogenic Hypertension

Zoccal

Machado

2011

Curr Hypertens Rep

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Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II-salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

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Section: Chemoreflex and Baroreflex After Chronic Intermittent Hypoxiacontrasting

confidence: 99%

Section: Chemoreflex and Baroreflex After Chronic Intermittent Hypoxiamentioning

confidence: 99%

Coupling Between Respiratory and Sympathetic Activities as a Novel Mechanism Underpinning Neurogenic Hypertension

Zoccal

Machado

2011

Curr Hypertens Rep

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“…Recently, Gu et al (25) demonstrated that impairment of baroreflex control of HR cannot be explained by baroreceptor afferents and vagal efferents because baroreceptor afferent function and vagal efferent control of HR are enhanced after CIH. Instead, a deficit in central autonomic components, possibly via cellular losses in the NA, could contribute to the reduced baroreflex control of HR (25,54). In the present study, we further demonstrated that CIH reduced the number of AMPA-and NMDA-immunoreactive neurons in NA.…”

Section: Perspectives and Significancesupporting

confidence: 60%

Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguus of F344 rats

Yan

Li²,

Harden³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Yan B, Li L, Harden SW, Gozal D, Lin Y, Wead WB, Wurster RD, Cheng ZJ. Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguus of F344 rats. Am J Physiol Regul Integr Comp Physiol 296: R299 -R308, 2009. First published November 19, 2008 doi:10.1152/ajpregu.90412.2008.-Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the nucleus ambiguus (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3-4 mo) were exposed to room air (RA) or CIH for 35-50 days (n ϭ 18/group). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (Ϫ200 m to ϩ200 m relative to caudal end of area postrema; n ϭ 6/group), and HR and arterial blood pressure responses were measured. In addition, brain stem sections at the level of Ϫ800, Ϫ400, 0, ϩ400, and ϩ800 m relative to obex were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA receptors and NMDA receptors (NMDARs) was quantified. Compared with RA, we found that after CIH 1) HR responses to microinjection of AMPA into the left NA were reduced (RA Ϫ290 Ϯ 30 vs. CIH Ϫ227 Ϯ 15 beats/min, P Ͻ 0.05); 2) HR responses to microinjection of NMDA into the left NA were reduced (RA Ϫ302 Ϯ 16 vs. CIH Ϫ238 Ϯ 27 beats/min, P Ͻ 0.05); and 3) the number of NMDAR1, AMPA GluR1, and AMPA GluR2/3-immunoreactive cells in the NA was reduced (P Ͻ 0.05). These results suggest that degeneration of NA neurons expressing GluRs contributes to impaired baroreflex control of HR in rats exposed to CIH. brain stem; parasympathetic efferent; heart; baroreflex; sleep apnea CHRONIC INTERMITTENT HYPOXIA (CIH) during sleep is now routinely used as a representative model for sleep apnea syndromes (20,36,43). In patients with obstructive sleep apnea, baroreflex control of heart rate (HR) is reduced (3, 4). In CIH-exposed rats and mice, CIH significantly reduced baroreflex control of HR (25,30,33). In addition, CIH decreased the central mediation of baroreflex bradycardia and conversely augmented the baroreceptor afferent function and the HR responses to electrical stimulation of the vagus nerve (25). These findings suggest that the impairment with CIH occurs within the brain stem and not in sensory or efferent premotor fibers.A substantial body of evidence indicates that the baroreflex control of HR is mediated through glutamate transmission in the nucleus ambiguus (NA) (46). Furthermore, the NA cardiac motoneurons express the ionotropic glutamate receptors ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AM...

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“…Thus, it is likely that the enhanced sympathetic activity along with the reduction of the baroreflex efficiency would impair the regulation of heart rate and the vasomotor tone of blood vessels eliciting hypertension. Besides that, it has been found that intermittent hypoxia produces parasympathetic withdrawal, attributed in part to neuronal loss in the vagal ambiguous nucleus (Lin et al, 2007, Yan et al, 2008.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress in the Carotid Body: Implications for the Cardioventilatory Alterations Induced by Obstructive Sleep Apnea

Iturriaga¹,

Río²

2012

Oxidative Stress and Diseases

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

Cited by 46 publications

References 43 publications

Coupling Between Respiratory and Sympathetic Activities as a Novel Mechanism Underpinning Neurogenic Hypertension

Coupling Between Respiratory and Sympathetic Activities as a Novel Mechanism Underpinning Neurogenic Hypertension

Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguus of F344 rats

Oxidative Stress in the Carotid Body: Implications for the Cardioventilatory Alterations Induced by Obstructive Sleep Apnea

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