Sympathetic nerve activity in obstructive sleep apnoea

Obstructive sleep apnea (OSA) is associated with increased sympathetic nerve activity, endothelial dysfunction, and premature cardiovascular disease. To determine whether hypoxia is associated with impaired skeletal muscle vasodilation, we compared femoral artery blood flow (ultrasound) and muscle sympathetic nerve activity (peroneal microneurography) during exposure to acute systemic hypoxia (fraction of inspired oxygen 0.1) in awake patients with OSA ( n = 10) and controls ( n = 8). To assess the role of elevated sympathetic nerve activity, in a separate group of patients with OSA ( n = 10) and controls ( n = 10) we measured brachial artery blood flow during hypoxia before and after regional α-adrenergic block with phentolamine. Despite elevated sympathetic activity, in OSA the vascular responses to hypoxia in the leg did not differ significantly from those in controls [ P = not significant (NS)]. Following regional phentolamine, in both groups the hypoxia-induced increase in brachial blood flow was markedly enhanced (OSA pre vs. post, 84 ± 13 vs. 201 ± 34 ml/min, P < 0.002; controls pre vs. post 62 ± 8 vs. 140 ± 26 ml/min, P < 0.01). At end hypoxia after phentolamine, the increase of brachial blood flow above baseline was similar (OSA vs. controls +61 ± 16 vs. +48 ± 6%; P = NS). We conclude that despite high sympathetic vasoconstrictor tone and prominent sympathetic responses to acute hypoxia, hypoxia-induced limb vasodilation is preserved in OSA.

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Periods of intermittent hypoxic apnea can alter chemoreflex control of sympathetic nerve activity in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00377.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. H2054-H2060 ◽

Cited By ~ 36

Author(s):

Michael J. Cutler ◽

Nicolette Muenter Swift ◽

David M. Keller ◽

Wendy L. Wasmund ◽

John R. Burk ◽

...

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Short Term ◽

Nerve Activity ◽

Treatment Groups ◽

Short Term Exposure ◽

Obstructive Sleep ◽

Main Effect ◽

Hypercapnic Hypoxia

Obstructive sleep apnea is associated with sustained elevation of muscle sympathetic nerve activity (MSNA) and altered chemoreflex control of MSNA, both of which likely play an important role in the development of hypertension in these patients. Additionally, short-term exposure to intermittent hypoxic apneas can produce a sustained elevation of MSNA. Therefore, we tested the hypothesis that 20 min of intermittent hypoxic apneas can alter chemoreflex control of MSNA. Twenty-one subjects were randomly assigned to one of three groups (hypoxic apnea, hypercapnic hypoxia, and isocapnic hypoxia). Subjects were exposed to 30 s of the perturbation every minute for 20 min. Chemoreflex control of MSNA was assessed during baseline, 1 min posttreatment, and every 15 min throughout 180 min of recovery by the MSNA response to a single hypoxic apnea. Recovery hypoxic apneas were matched to a baseline hypoxic apnea with a similar nadir oxygen saturation. A significant main effect for chemoreflex control of MSNA was observed after 20 min of intermittent hypoxic apneas ( P < 0.001). The MSNA response to a single hypoxic apnea was attenuated 1 min postexposure compared with baseline ( P < 0.001), became augmented within 30 min of recovery, and remained augmented through 165 min of recovery ( P < 0.05). Comparison of treatment groups revealed no differences in the chemoreflex control of MSNA during recovery ( P = 0.69). These data support the hypothesis that 20 min of intermittent hypoxic apneas can alter chemoreflex control of MSNA. Furthermore, this response appears to be mediated by hypoxia.

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Neurocirculatory consequences of negative intrathoracic pressure vs. asphyxia during voluntary apnea

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.6.2969 ◽

1993 ◽

Vol 74 (6) ◽

pp. 2969-2975 ◽

Cited By ~ 121

Author(s):

B. J. Morgan ◽

T. Denahan ◽

T. J. Ebert

Keyword(s):

Arterial Pressure ◽

Sympathetic Nerve ◽

Sleep Disordered Breathing ◽

Sympathetic Nerve Activity ◽

Intrathoracic Pressure ◽

Sympathetic Activation ◽

Nerve Activity ◽

Primary Mechanism ◽

Obstructive Sleep ◽

Voluntary Apnea

To investigate the mechanisms responsible for fluctuations in arterial pressure and sympathetic nerve activity that occur during obstructive sleep apnea, we studied neurocirculatory responses to Mueller maneuvers and breath holds in conscious humans. During 20-s Mueller maneuvers at -40 mmHg, mean arterial pressure fell initially (-11 +/- 3 mmHg) and then rose above baseline (+8 +/- 3 mmHg) on release of the inspiratory strain. Sympathetic outflow to skeletal muscle was almost completely suppressed during the initial moments of the maneuver and rose to more than three times the baseline level at the termination of the maneuver. Simple 20-s breath holds were accompanied by time-dependent increases in both arterial pressure (+11 +/- 3 mmHg) and sympathetic nerve activity (> 3 times baseline). The administration of supplemental O2 greatly attenuated the increases in arterial pressure and sympathetic nerve activity during Mueller maneuvers and breath holds. We conclude that carotid chemoreflex stimulation is the primary mechanism responsible for apnea-induced sympathetic activation during wakefulness and that it may contribute importantly to the sympathetic activation that accompanies sleep-disordered breathing.

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A projection from the hypothalamic paraventricular nucleus to the nucleus tractus solitarii is critical for cardiorespiratory responses to hypoxia

10.32469/10355/70031 ◽

2019 ◽

Author(s):

◽

Brian Ruyle

Keyword(s):

Paraventricular Nucleus ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Nucleus Tractus Solitarii ◽

Reflex Response ◽

Protective Mechanism ◽

Adaptive Responses ◽

Nerve Activity ◽

Cardiorespiratory Responses ◽

Obstructive Sleep

The arterial chemoreflex is an essential protective mechanism for adaptive responses to hypoxia. Stimulation of peripheral chemoreceptors initiates a reflex response that generates compensatory physiological responses, including increased ventilation, arterial pressure and sympathetic nerve activity. However, chemoreflex dysfunction, including over-excitation of chemoreflex pathways, leads to respiratory instability and increased sympathetic nerve activity (SNA) in disease states including heart failure, hypertension and obstructive sleep apnea (170, 199, 232). Determining the mechanisms involved in the central chemoreflex neurocircuitry and its plasticity in health and disease may lead to the development of targeted therapies in cardiorespiratory disease. This dissertation seeks to provide new insight into the neural circuits that drive chemoreflex function. Compensatory responses to chemoreflex stimulation are generated through coordinated interactions between nuclei in the brainstem, forebrain and spinal cord. However, the underlying neurocircuitry, including relevant connections between these nuclei, and the signaling mechanisms that take place within each region are not completely understood. The nucleus tractus solitarii (nTS) and the paraventricular nucleus (PVN) are two central nuclei known to drive chemoreflex function and are implicated in altered cardiorespiratory responses resulting from chemoreflex dysfunction. These two regions form reciprocal connections but the extent to which these connections influence cardiorespiratory regulation and specifically chemoreflex function is unclear. The overarching goal of this dissertation is to examine whether a population of PVN neurons that project to the nTS is involved in shaping cardiorespiratory responses to chemorefle activation by hypoxia. The experiments performed in the three studies (Chapters 2-4) test the overall hypothesis that a descending PVN-nTS projection is an essential component of chemoreflex neurocircuitry; chemoreflex-evoked activation of this pathway is critical for compensatory cardiorespiratory responses to hypoxia.

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