Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA ( r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.

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Sympathetic neural responses to sleep disorders and insufficiencies

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00590.2021 ◽

2022 ◽

Author(s):

Ian M. Greenlund ◽

Jason R. Carter

Keyword(s):

Sleep Deprivation ◽

Sleep Disorders ◽

Sleep Duration ◽

Muscle Sympathetic Nerve Activity ◽

Experimental Models ◽

Plasma Norepinephrine ◽

Poor Sleep ◽

Short Sleep Duration ◽

Short Sleep ◽

Obstructive Sleep

Short sleep duration and poor sleep quality are associated with cardiovascular risk, and sympathetic nervous system (SNS) dysfunction appears to be a key contributor. The present review will characterize sympathetic function across several sleep disorders and insufficiencies in humans, including sleep deprivation, insomnia, narcolepsy, and obstructive sleep apnea (OSA). We will focus on direct assessments of sympathetic activation (e.g., plasma norepinephrine and muscle sympathetic nerve activity), but include heart rate variability (HRV) when direct assessments are lacking. The review also emphasizes sex as a key biological variable. Experimental models of total sleep deprivation and sleep restriction are converging to support epidemiological studies reporting an association between short sleep duration and hypertension, especially in women. A systemic increase of SNS activity via plasma norepinephrine is present with insomnia, and has also been confirmed with direct, regionally-specific evidence from microneurographic studies. Narcolepsy is characterized by autonomic dysfunction via both HRV and microneurographic studies, but with opposing conclusions regarding SNS activation. Robust sympathoexcitation is well documented in OSA, and is related to baroreflex and chemoreflex dysfunction. Treatment of OSA with continuous positive airway pressure results in sympathoinhibition. In summary, sleep disorders and insufficiencies are often characterized by sympathoexcitation and/or sympathetic/baroreflex dysfunction, with several studies suggesting women may be at heightened risk.

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Abstract P545: Insufficient Sleep and Nitric Oxide-Mediated Endothelium-Dependent Vasodilation in Adults With Elevated Blood Pressure

Circulation ◽

10.1161/circ.141.suppl_1.p545 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Kelly A Stockelman ◽

Anthony R Bain ◽

Dana M Withrow ◽

Tracey A Larson ◽

Elizabeth M Boland ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Blood Pressure ◽

Sleep Duration ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Short Sleep Duration ◽

Insufficient Sleep ◽

Short Sleep ◽

Normal Sleep

Elevated blood pressure (BP ≥130/80 mmHg) is associated with increased risk for myocardial infarction, heart failure, stroke and vascular disease. Insufficient nightly sleep (<7 h/night) has been linked not only to the etiology of elevated blood pressure but is a prevalent, often ignored, comorbidity. Indeed, short sleep duration is now considered to be a plausible risk factor for elevated blood pressure and a harbinger of increased cardiovascular risk. A high prevalence of insufficient nightly sleep has been reported in adults with elevated blood pressure. The influence of insufficient sleep on endothelial vasodilator function in adults with elevated blood pressure is unknown. We tested the hypotheses that chronic insufficient sleep is associated with diminished nitric oxide (NO)-mediated endothelium-dependent vasodilation in adults with elevated blood pressure. Moreover, the insufficient sleep-related reduction in endothelial vasodilator function is due, at least in part to increased oxidative stress. Thirty-five middle-aged and older adults with elevated blood pressure were studied: 15 with normal nightly sleep duration (11M/4F; age: 58±2 yr; BP: 136/82±1/2 mmHg; sleep: 7.6±0.2 h/night) and 20 with short nightly sleep duration (14M/6F; 58±1 yr; BP: 138/84±1/1 mmHg; sleep: 6.0±0.1 h/night). Forearm blood flow (FBF) responses to intra-arterial infusion of acetylcholine (ACh), in the absence and presence of the endothelial NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA) and the antioxidant vitamin C were determined by venous occlusion plethysmography. The FBF response to ACh was significantly lower (~20%) in the short sleep (from 3.8±0.2 to 11.0±0.6 ml/100 ml tissue/min) compared with the normal sleep duration group (from 4.2±0.2 to 13.6±0.6 ml/100 ml tissue/min). L-NMMA significantly reduced (~25%) the FBF response to ACh in the normal sleep but not the short sleep group. Vitamin C markedly increased (~35%; P<0.05) the vasodilator response to ACh in short sleepers only. In summary, habitual short sleep duration worsens NO-mediated endothelium-dependent vasodilation in adults with elevated blood pressure. Furthermore, the sleep-related diminishment in endothelial vasodilator function is due, in part, to increased oxidative stress.

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Sleep deprivation and obesity in adults: a brief narrative review

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2018-000392 ◽

2018 ◽

Vol 4 (1) ◽

pp. e000392 ◽

Cited By ~ 10

Author(s):

Christopher B Cooper ◽

Eric V Neufeld ◽

Brett A Dolezal ◽

Jennifer L Martin

Keyword(s):

Sleep Deprivation ◽

Short Communication ◽

Sleep Restriction ◽

Short Sleep Duration ◽

Short Sleep ◽

The Usa ◽

Average Body Mass ◽

Body Mass Indexes ◽

Developed Nations ◽

Average Body

Background/aimsObesity and sleep deprivation are two epidemics that pervade developed nations. Their rates have been steadily rising worldwide, especially in the USA. This short communication will explore the link between the two conditions and outline the proposed mechanisms behind their relationship.MethodsStudies on the topic of sleep and obesity were reviewed, and findings were used to develop a theoretical model for the biological link between short sleep duration and obesity.ResultsIndividuals who regularly slept less than 7 hours per night were more likely to have higher average body mass indexes and develop obesity than those who slept more. Studies showed that experimental sleep restriction was associated with increased levels of ghrelin, salt retention and inflammatory markers as well as decreased levels of leptin and insulin sensitivity.ConclusionsThere may be a link between obesity and sleep deprivation. We recommend further investigations are to elucidate the potential mechanisms.

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Insomnia and sleep state misperception: Clinical features, diagnosis, management and implications

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1696 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s853-s853

Author(s):

J. Isaac ◽

C. Santos ◽

A. Matos Pires

Keyword(s):

Sleep Duration ◽

Clinical Features ◽

Mental Disease ◽

Sleep Time ◽

Sleep State ◽

Short Sleep Duration ◽

Short Sleep ◽

Psychological Therapies ◽

Normal Sleep ◽

Competing Interest

BackgroundInsomnia is a highly prevalent complaint, largely associated with mental disease. Clinical evidence classifies insomnia in 2 subtypes: with sleep misperception (WSM) and without sleep misperception (wSM). That presents distinctive pathophysiologic pathways and different public health implications.ObjectivesDescribe the main differences between primary insomnia WSM and wSM regarding:– clinical features;– diagnosis;– management;– implications.MethodsWe conducted a systematic review. PubMed, Embase and PsycInfo were searched from 2000–2016. The reference lists of systematic reviews, narrative synthesis and some important articles were included. Following the inclusion criteria, we selected 25 studies from 59 articles.ResultsThe prevalence of sleep-state misperception in primary insomniacs (total sleep time > 6.5 h and sleep efficiency > 85%) is around 26%. Insomniacs with normal sleep duration showed a profile of high depression and anxiety and low ego strength, whereas insomniacs with short sleep duration showed a profile of a medical disorder.Cortical hyperarousal is higher in insomniacs and could be related to an alteration in sleep protection mechanisms. The sleep architecture was relatively normal for the WSM comparing with the group wSM. Risk of cardiometabolic, neurocognitive morbidity and mortality, and responses to treatment are different between these two insomnia phenotypes. Patients with short sleep duration may respond better to biological treatments, whereas insomnia with normal sleep duration may respond primarily to psychological therapies.ConclusionsThe clinical characteristics of patients with sleep-state misperception differed from those without this condition. Available research related to these conditions is expanding rapidly, but many questions remain unanswered.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Total sleep deprivation alters cardiovascular reactivity to acute stressors in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00561.2012 ◽

2012 ◽

Vol 113 (6) ◽

pp. 903-908 ◽

Cited By ~ 27

Author(s):

Huan Yang ◽

John J. Durocher ◽

Robert A. Larson ◽

Joseph P. DellaValla ◽

Jason R. Carter

Keyword(s):

Sex Differences ◽

Sleep Deprivation ◽

Cardiovascular Reactivity ◽

Muscle Sympathetic Nerve Activity ◽

Cold Pressor Test ◽

Cold Pressor ◽

Epidemiological Studies ◽

Total Sleep Deprivation ◽

Increased Risk ◽

Forearm Vascular Conductance

Exaggerated cardiovascular reactivity to mental stress (MS) and cold pressor test (CPT) has been linked to increased risk of cardiovascular disease. Recent epidemiological studies identify sleep deprivation as an important risk factor for hypertension, yet the relations between sleep deprivation and cardiovascular reactivity remain equivocal. We hypothesized that 24-h total sleep deprivation (TSD) would augment cardiovascular reactivity to MS and CPT and blunt the MS-induced forearm vasodilation. Because the associations between TSD and hypertension appear to be stronger in women, a secondary aim was to probe for sex differences. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were recorded during MS and CPT in 28 young, healthy subjects (14 men and 14 women) after normal sleep (NS) and 24-h TSD (randomized, crossover design). Forearm vascular conductance (FVC) was recorded during MS. MAP, FVC, and MSNA ( n = 10) responses to MS were not different between NS and TSD (condition × time, P > 0.05). Likewise, MAP and MSNA ( n = 6) responses to CPT were not different between NS and TSD (condition × time, P > 0.05). In contrast, increases in HR during both MS and CPT were augmented after TSD (condition × time, P ≤ 0.05), and these augmented HR responses persisted during both recoveries. When analyzed for sex differences, cardiovascular reactivity to MS and CPT was not different between sexes (condition × time × sex, P > 0.05). We conclude that TSD does not significantly alter MAP, MSNA, or forearm vascular responses to MS and CPT. The augmented tachycardia responses during and after both acute stressors provide new insight regarding the emerging links among sleep deprivation, stress, and cardiovascular risk.

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Abstract 2455: Short Sleep Duration is an Independent Predictor of Cardiovascular Events in Hypertensive Patients

Circulation ◽

10.1161/circ.118.suppl_18.s_728-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Kazuo Eguchi ◽

Thomas G Pickering ◽

Joseph E Schwartz ◽

Satoshi Hoshide ◽

Joji Ishikawa ◽

...

Keyword(s):

Sleep Duration ◽

Short Duration ◽

Cardiovascular Events ◽

Sleep Time ◽

Cvd Risk ◽

Short Sleep Duration ◽

Hypertensive Patients ◽

Short Sleep ◽

Multivariable Analyses ◽

Normal Sleep

We aimed this study to test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD) in hypertensive patients. We performed ambulatory BP monitoring (ABPM) in 1255 subjects with hypertension (mean age: 70.4 ± 9.9 years) and they were followed for an average of 50 ± 23 months. Short sleep duration was defined as <7.5 hrs (20 th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio (HR) and 95% CI for short sleep duration. A riser pattern was defined when average nighttime SBP exceeded daytime SBP. The end point was cardiovascular events: stroke, fatal or non-fatal myocardial infarction (MI), and sudden cardiac death. In multivariable analyses, short duration of sleep (<7.5 hrs) was associated with incident CVD (HR=1.68; 1.06 –2.66, P=.03). A synergistic interaction was observed between short sleep duration and the riser pattern (P=.089). When subjects were categorized on the basis of their sleep time and riser/non-riser patterns, the shorter sleep+riser group had a highest incidence of CVD among the 4 groups ( Figure ), and substantially and significantly higher incidence of CVD than the predominant normal sleep+non-riser group (HR=4.43; 2.09 –9.39, P<0.001), independent of covariates. Short duration of sleep is associated with incident CVD risk, and the combination of riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of hypertensive patients.

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Abstract P183: Influence of Insufficient Sleep on Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Hypertension ◽

10.1161/hyp.70.suppl_1.p183 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Anthony R Bain ◽

Caitlin A Dow ◽

Kyle J Diehl ◽

Tyler D Bammert ◽

Jared J Greiner ◽

...

Keyword(s):

Sleep Duration ◽

Tissue Type ◽

Short Sleep Duration ◽

Insufficient Sleep ◽

Short Sleep ◽

Type Plasminogen Activator ◽

Increased Risk ◽

Normal Sleep ◽

Middle Aged Adults

The capacity of the endothelium to release tissue-type plasminogen activator (t-PA) is impaired in adults with elevated BP, leading to an increased risk of thrombotic events. Insufficient sleep is independently associated with elevated BP and impaired t-PA release. However, the compounded influence of insufficient sleep on t-PA release in adults with elevated BP is unknown. We tested the hypothesis that impairments in the capacity of the endothelium to release t-PA in adults with elevated BP is worse in those who sleep <7 h/night (short sleep duration) compared with those who sleep 7 to 9 h/night (normal sleep duration). We studied 38 sedentary, middle-aged adults: 10 with normal BP and normal nightly sleep duration (6M/4F; age: 55±2 yr; BP: 114/94±2/3 mmHg, sleep duration: 7.4±0.2 h); 14 with elevated BP and normal nightly sleep duration (8M/6F; 60±2 yr; 141/87±2/2 mmHg; 7.8±0.1 h); and 14 with elevated BP and short nightly sleep duration (10M/4F; 57±2 yr; 139/85±2/2 mmHg; 6.1±0.2 h). All subjects were free of overt metabolic and coronary disease. Net endothelial release of t-PA was determined, in vivo, in response to intra-brachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2.0-8.0 μg/min). In the normal sleep groups, as expected, endothelial t-PA release in response to BK was significantly blunted (~30%) in the adults with elevated BP (from -1.2±0.8 to 50.2±4.8 ng/100mL tissue/min) compared with normal BP (from 0.9±3.4 to 73.0±8.0 ng/100mL tissue/min); and total t-PA release (area under the BK curve) was ~25% lower (p<0.05) in the adults with elevated (307±33 ng/100mL tissue) vs. normal (396±27 ng/100mL tissue) BP. Importantly, net endothelial release rate (from -1.5±1.0 to 40.6±4.3 ng/100mL tissue/min) and total amount of t-PA released (222±28 ng/100mL tissue) in response to BK were markedly lower (~25% and 30%, respectively, P<0.05) in the elevated BP and short sleep duration group compared with the elevated BP and normal sleep duration group. In the elevated BP population, sleep duration was positively correlated with total t-PA release (r=0.46, P<0.05). There was no effect of SNP on t-PA release in any group. In summary, insufficient sleep is associated with exacerbated impairments in t-PA release in adults with elevated BP.

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Abstract 28: Regular Aerobic Exercise Counteracts Endothelial Vasomotor Dysfunction Associated With Insufficient Sleep

Circulation ◽

10.1161/circ.141.suppl_1.28 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Kelly A Stockelman ◽

Anthony R Bain ◽

Caitlin A Dow ◽

Jared J Greiner ◽

Brian L Stauffer ◽

...

Keyword(s):

Exercise Training ◽

Aerobic Exercise ◽

Sleep Duration ◽

Middle Aged ◽

Short Sleep Duration ◽

Insufficient Sleep ◽

Short Sleep ◽

Vasomotor Regulation ◽

Normal Sleep ◽

Middle Aged Adults

Insufficient sleep, defined as chronic short sleep duration (<7 h/night), is an independent risk factor for cardiovascular disease (CVD). We have previously demonstrated that insufficient sleep is associated with reduced endothelium-dependent vasodilation and enhanced endothelin (ET)-1-mediated vasoconstrictor tone. Impaired endothelial vasomotor regulation is thought to contribute mechanistically to the increased risk of atherosclerotic vascular disease incurred with chronic insufficient sleep. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn reducing cardiovascular risk. It is currently unknown if regular aerobic exercise can counteract the negative impact of insufficient sleep on endothelial vasomotor regulation. We tested the hypotheses that regular aerobic exercise would: 1) improve endothelial vasodilation; and 2) decrease ET-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep less than 7 h/night. We studied 36 healthy, middle-aged adults: 16 with normal sleep duration (10M/6F; age: 57±2 yr; sleep duration: 7.4±0.1 h/night) and 20 with short sleep duration (11M/9F; 56±1 yr; sleep duration: 6.2±0.1 h/night). The 20 short sleepers completed a 3-month aerobic exercise training intervention. Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial doses of acetylcholine (ACh), sodium nitroprusside (SNP), BQ-123 (ET A receptor antagonist) and ACh + BQ-123 in both groups and after the exercise intervention in the short sleepers. As expected, forearm vasodilator responses to ACh were lower (20%; P<0.05) in the short (from 4.2±0.2 to 10.5±0.6 mL/100 mL tissue/min) vs normal (4.2±0.2 to 12.7±0.6 mL/100 mL tissue/min) sleepers. FBF responses to SNP were comparable between the groups. In response to BQ-123, short sleep group had a greater increase in resting FBF than normal sleep group (~25% vs ~8%; P< 0.05). ACh+BQ-123 resulted in an ~25% increase in the ACh-vasodilation in the short sleep group only. After exercise training, although nightly sleep duration was not affected (6.4±0.1 h/night), ACh-mediated vasodilation was ~20% higher (P<0.05), ET-1-mediated vasoconstriction was ~90% lower (P<0.05) and vasodilator response to ACh was not significantly increased with ET A receptor blockade. These results indicate that regular aerobic exercise can reverse the negative influence of insufficient sleep on endothelial vasomotor function, independent of changes in nightly sleep duration.

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