Reversal of functional changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea following CPAP

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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Reversal of functional changes in the brain associated with obstructive sleep apnoea following 6 months of CPAP

NeuroImage Clinical ◽

10.1016/j.nicl.2015.02.010 ◽

2015 ◽

Vol 7 ◽

pp. 799-806 ◽

Cited By ~ 16

Author(s):

Rania H. Fatouleh ◽

Linda C. Lundblad ◽

Paul M. Macey ◽

David K. McKenzie ◽

Luke A. Henderson ◽

...

Keyword(s):

Obstructive Sleep Apnoea ◽

Sleep Apnoea ◽

Functional Changes ◽

Obstructive Sleep ◽

The Brain

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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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Abstract 019: Effect of CPAP on Blood Pressure and Central Sympathetic Outflow in Diabetic Patients with OSA, Resistant HTN, and CKD

Hypertension ◽

10.1161/hyp.70.suppl_1.019 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Marcel Ruzicka ◽

Swapnil Hiremath ◽

Frans H Leenens ◽

Judith Leech ◽

Shawn Aaron

Keyword(s):

Blood Pressure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Plasma Catecholamines ◽

Response To Treatment ◽

Diabetic Patients ◽

Nerve Activity ◽

Sympathetic Hyperactivity ◽

Obstructive Sleep

Introduction: Central sympathetic hyperactivity as assessed by muscle sympathetic nerve activity recordings is thought to play a crucial role in the development and maintenance of hypertension (HTN) in patients with obstructive sleep apnea (OSA). Decreases in daytime and nocturnal blood pressure (BP) in response to treatment with continuous positive airway pressure (CPAP) are paralleled by decreases in muscle sympathetic nerve activity (MSNA). Patients with chronic kidney disease (CKD) have high MSNA. Bilateral nephrectomy, but not renal transplantation normalizes MSNA indicating central sympathoexcitatory effects by renal afferents. The objective of this study was to assess to what extent is HTN driven by central sympathetic hyperactivity in patients with diabetic CKD, OSA, and resistant HTN. Thirteen patients (age 62.2±7.4 years) with diabetic CKD, resistant HTN defined as SBP on 24-hr ABPM above 135 mmHg while on 3 or more BP lowering drugs (including diuretic) with OSA, were randomized to therapeutic CPAP or non-therapeutic CPAP for one months. 24-hr ABPM, plasma catecholamines, aldosterone, and renin, and MSNA were assessed before and 1 months after randomization. Our results show (Table) that in contrast to sham CPAP, therapeutic CPAP decreased daytime and nighttime BP. In contrast, neither therapeutic nor sham CPAP caused any changes in MSNA and plasma catecholamines. In conclusion, decreases in BP in response to CPAP in patients with in diabetic CKD, despite maintained high MSNA, indicate other mechanism contributing to HTN in these patients as well as other central sympathoexcitatory pathways activated.

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Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia

Journal of Applied Physiology ◽

10.1152/jappl.1995.79.2.581 ◽

1995 ◽

Vol 79 (2) ◽

pp. 581-588 ◽

Cited By ~ 179

Author(s):

U. Leuenberger ◽

E. Jacob ◽

L. Sweer ◽

N. Waravdekar ◽

C. Zwillich ◽

...

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Matched Control ◽

Sleep Stage ◽

Muscle Sympathetic Nerve Activity ◽

Nerve Activity ◽

Obstructive Apnea ◽

Arterial Blood ◽

Obstructive Sleep

Obstructive sleep apnea (OSA) is associated with oscillations of arterial blood pressure (BP) that occur in phase with irregularities of respiration. To explore the role of the sympathetic nervous system in these responses, we studied muscle sympathetic nerve activity (MSNA; peroneal microneurography), an index of vasoconstrictor nerve traffic, and BP during awake regular breathing and during spontaneous apneas in patients with OSA. To determine the role of the arterial chemoreflex, we also examined the effects of 100% O2 (hyperoxia) on MSNA and BP. In awake regularly breathing patients with OSA (n = 12), resting MSNA was markedly higher than in an age-matched control population (n = 15) [41 +/- 23 (SD) vs. 24 +/- 17 bursts/min; P < 0.05] and was unchanged during hyperoxia (n = 9). Apneas during sleep (n = 8) were associated with surges in MSNA followed by transient rises in BP when breathing resumed. In contrast to room air apneas, hyperoxic apneas of similar duration were associated with attenuated MSNA responses (+82 +/- 84% vs. +5 +/- 25% compared with awake baseline; P < 0.05; n = 6), even though O2 did not affect sleep stage and the occurrence of arousal. Thus the BP oscillations that occur with apnea during sleep may in part be mediated by intermittent surges of sympathetic activity resulting in vasoconstriction. Because the MSNA responses to obstructive apnea are blunted during O2 administration, they appear to be linked to intermittent arterial hypoxemia and stimulation of arterial chemoreceptors.

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