Dataset Information

Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism.

ABSTRACT:

Study objectives

Sleep loss is suspected to induce endothelial dysfunction, a key factor in cardiovascular risk. We examined whether sympathetic activity is involved in the endothelial dysfunction caused by total sleep deprivation (TSD).

Design

TWO GROUPS: TSD (24-h wakefulness), using slowly rotating wheels, and wheel control (WC).

Participants

Seven-month-old male Wistar rats.

Interventions

Pharmacological sympathectomy (reserpine, 5 mg/kg, intraperitoneal), nitric oxide synthase (NOS) inhibition (N (G)-nitro-L-arginine, 20 mg/kg, intraperitoneally 30 min before experiment) and cyclooxygenase (COX) inhibition (indomethacin, 5 mg/kg, intraperitoneally 30 min before experiment).

Measurements and results

In protocol 1, changes in heart rate (HR) and blood pressure were continuously recorded in the sympathectomized and non-sympathectomized rats. Blood pressure and HR increased during TSD in non-sympathectomized rats. In protocol 2, changes in skin blood flow (vasodilation) were assessed in the sympathectomized and non-sympathectomized rats using laser-Doppler flowmetry coupled with iontophoretic delivery of acetylcholine (ACh), sodium nitroprusside (SNP), and anodal and cathodal currents. ACh- and cathodal current-induced vasodilations were significantly attenuated after TSD in non-sympathectomized and sympathectomized rats (51% and 60%, respectively). In protocol 3, ACh-induced vasodilation was attenuated after NOS and COX inhibition (66% and 49%, respectively). Cathodal current-induced vasodilation decreased by 40% after COX inhibition. In TSD compared to WC a decrease in ACh-induced vasodilation was still observed after COX inhibition. No changes in SNP- and anodal current-induced vasodilation were detected.

Conclusion

These results demonstrate that total sleep deprivation induces a reduction in endothelial-dependent vasodilation. This endothelial dysfunction is independent of blood pressure and sympathetic activity but associated with nitric oxide synthase and cyclooxygenase pathway alterations.

SUBMITTER: Sauvet F

PROVIDER: S-EPMC3920311 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism.

Sauvet Fabien F Florence Geneviève G Van Beers Pascal P Drogou Catherine C Lagrume Christophe C Chaumes Cyrielle C Ciret Sylvain S Leftheriotis Georges G Chennaoui Mounir M

Sleep 20140301 3

<h4>Study objectives</h4>Sleep loss is suspected to induce endothelial dysfunction, a key factor in cardiovascular risk. We examined whether sympathetic activity is involved in the endothelial dysfunction caused by total sleep deprivation (TSD).<h4>Design</h4>TWO GROUPS: TSD (24-h wakefulness), using slowly rotating wheels, and wheel control (WC).<h4>Participants</h4>Seven-month-old male Wistar rats.<h4>Interventions</h4>Pharmacological sympathectomy (reserpine, 5 mg/kg, intraperitoneal), nitric ...[more]

PMID: 24587568

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Project description:Introduction: Sleep deprivation is associated with increased cardiovascular risk, which is more pronounced in women than men; however, causal evidence is lacking and the underlying mechanisms are unclear. We used randomized crossover design of prolonged sleep deprivation that mimics “life-like conditions” and endothelial cells (ECs) harvested from healthy women to investigate directly whether sleep deprivation impairs endothelial function and to identify underlying mechanisms. Methods: Healthy women with normal habitual sleep (7-9 h/day) were randomly allocated to 6-weeks of adequate sleep (7-9 h/day) or sleep deprivation (1.5 h less than habitual sleep) in a crossover design. Sleep duration was monitored objectively by actigraphy. EC harvesting and brachial artery flow-mediated dilation (FMD) were performed at baseline and the end of adequate sleep and sleep deprivation period. Results: Twenty-eight healthy women (mean [SE] age 35±13 years; BMI 25±3 kg/m2) participated. Compared with adequate sleep, sleep deprivation reduced FMD (mean±SE 8.65±0.48 vs. 7.35±0.39, p=0.02) and increased EC inflammation (nuclear factor-κB nuclear fluorescence area mean±SE 1.36±0.24 vs. 2.04±0.38 μm2, p=0.03 and mRNA expression of vascular cell adhesion molecule-1 mean±SE 1.00±0.19 vs. 2.31±0.72, p=0.04) compared with adequate sleep. Sleep deprivation increased EC oxidative stress by 67% compared with adequate sleep (redox sensitive fluorogenic probe fluorescence intensity, p=0.002) without upregulating antioxidant response. Using RNA-seq and a predicted protein-protein interaction algorithm, we identified reduced expression of serum response factor, a transcription factor that primes cortical response to sleep deprivation, and its endothelial target Defective in Cullin Neddylation-1 Domain Containing 3 as novel mediators of impaired nuclear factor (erythroid-derived 2)-like 2-mediated antioxidant responses in ECs in sleep deprivation. Conclusion: Sleep deprivation impairs clearance of endothelial oxidant stress accumulated during wakefulness leading to endothelial dysfunction and potentially increased cardiovascular risk in women. Trial Registration Number: ClinicalTrials.gov NCT02835261

Dataset Information

Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism.

Study objectives

Design

Participants

Interventions

Measurements and results

Conclusion

Publications

Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism.

Similar Datasets

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