Arousal From Sleep and Sympathetic Excitation During Wakefulness

Abstract

Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity. Polysomnography identified 24 as having either no or mild obstructive sleep apnea (apnea–hypopnea index <15 events/h) and 24 with moderate-to-severe obstructive sleep apnea (apnea–hypopnea index >15 events/h). Burst incidence correlated significantly with arousal index ( r =0.53; P <0.001), minimum oxygen saturation ( r =−0.43; P =0.002), apnea–hypopnea index ( r =0.41; P =0.004), age ( r =0.36; P =0.013), and body mass index ( r =0.33; P =0.022) but not with oxygen desaturation index ( r =0.28; P =0.056). Arousal index was the single strongest predictor of muscle sympathetic nerve activity burst incidence, present in all best subsets regression models. The model with the highest adjusted R 2 (0.456) incorporated arousal index, minimum oxygen saturation, age, body mass index, and oxygen desaturation index but not apnea–hypopnea index. An apnea- and hypoxia-independent effect of sleep fragmentation on sympathetic discharge during wakefulness could contribute to intersubject variability, age-related increases in muscle sympathetic nerve activity, associations between sleep deprivation and insulin resistance or insomnia and future cardiovascular events, and residual adrenergic risk with persistence of hypertension should therapy eliminate obstructive apneas but not arousals.

Sympathoexcitation following intermittent hypoxia in rat is mediated by circulating angiotensin II acting at the carotid body and subfornical organ

“…The present study demonstrates the importance of the RAS for the sympathetic effects of AIH and suggests that transient repeated surges in Ang II cause immediate increases in SNA. The relationship between recurrent hypoxia and transient RAS activation may contribute to the association between apnoea/hypopnea index and daytime SNA in humans with obstructive sleep aponea (Peppard et al 2000;Taylor et al 2016). We also show that the sympathetic effects of AIH require both the CB and SFO and also that AIH has sympathetic effects in CB denervated rats.…”

“…; Taylor et al . ). We also show that the sympathetic effects of AIH require both the CB and SFO and also that AIH has sympathetic effects in CB denervated rats.…”

“…; Taylor et al . ). Similarly, adult rodents exposed to chronic intermittent hypoxia (CIH) develop hypertension (Fletcher et al .…”

“…Chronic elevations in the activity of the sympathetic nerves controlling the cardiovascular system are a pathophysiological characteristic of neurogenic hypertension (Esler, 2010). In patients with obstructive sleep apnoea, there is evidence suggesting that recurrent hypoxemia during sleep contributes to the elevation in daytime sympathetic nerve activity (SNA) and hypertension associated with this condition (Peppard et al 2000;Taylor et al 2016). Similarly, adult rodents exposed to chronic intermittent hypoxia (CIH) develop hypertension (Fletcher et al 1992a(Fletcher et al , b, 1999Zoccal et al 2007;Del Rio et al 2016) and increased sensitivity of sympathoexcitatory reflexes (Huang et al 2009;Silva & Schreihofer, 2011).…”

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability

“…However, we cannot exclude that other mechanisms may contribute to the aberrant cardiac autonomic modulation seen in patients with OSA and PLMS. For instance, although the arousal index was not significantly related to HRV variables, there may be residual effects of event‐related arousals, which are known to be accompanied by sympathetic activation (Taylor et al., ). It is plausible that, in patients with both OSA and PLMS, greater sleep fragmentation due to the combination of repetitive respiratory and LM events may result in excessive sympathetic excitation, thus generating abnormal HRV compared with patients with only OSA or PLMS.…”