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

• Published in: Sleep (New York, N.Y.) Vol. 37; no. 3; pp. 465 - 473
• Main Authors: Sauvet, Fabien, Florence, Geneviève, Van Beers, Pascal, Drogou, Catherine, Lagrume, Christophe, Chaumes, Cyrielle, Ciret, Sylvain, Leftheriotis, Georges, Chennaoui, Mounir
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-03-2014; Associated Professional Sleep Societies, LLC
• Subjects: Acetylcholine - pharmacology; Animals; Blood Pressure; Body Temperature; Cardiovascular Diseases - enzymology; Cardiovascular Diseases - etiology; Cardiovascular Diseases - pathology; Cardiovascular Diseases - physiopathology; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - pharmacology; Epoprostenol - metabolism; Heart Rate; Laser-Doppler Flowmetry; Life Sciences; Male; Metabolic Networks and Pathways; Nitric Oxide Synthase - metabolism; Nitroprusside - pharmacology; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Wistar; Skin - blood supply; Sleep Deprivation - complications; Sleep Deprivation - enzymology; Sleep Deprivation - physiopathology; Sympathectomy; Sympathetic Nervous System; Total Sleep Deprivation Alters Endothelial Function in Rats; Vasodilation; skin blood flow; arterial pressure; sodium nitroprusside; current-induced vasodilation; sympathectomy; vascular reactivity; Acetylcholine; endothelial dysfunction; iontophoresis
• ISSN: 0161-8105; 1550-9109
• DOI: 10.5665/sleep.3476

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).
TWO GROUPS: TSD (24-h wakefulness), using slowly rotating wheels, and wheel control (WC).
Seven-month-old male Wistar rats.
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).
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.
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.