title: Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  TWO GROUPS: TSD (24-h wakefulness), using slowly rotating wheels, and wheel control (WC).
  
  
  METHODS
  Seven-month-old male Wistar rats.
  
  
  METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Sauvet
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Florence
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Van Beers
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Drogou
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lagrume
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Chaumes
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ciret
authors.affiliation: University of Angers, Angers, France ; Unité mixte Centre National de la Recherche Scientifique (CNRS) 6214 - Institut National de la Santé et de la Recherche Médicale (INSERM) 771, Angers, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Leftheriotis
authors.affiliation: Armed Forces Biomedical Research Institute (IRBA), Brétigny-sur-Orge, France.
authors.forename: Mounir
authors.initials: M
authors.lastname: Chennaoui
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D006339:Heart Rate; D017078:Laser-Doppler Flowmetry; D008297:Male; D053858:Metabolic Networks and Pathways; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply; D012892:Sleep Deprivation / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology*; D013562:Sympathectomy; D013564:Sympathetic Nervous System; D014664:Vasodilation
chemical_list: D004791:Enzyme Inhibitors; D009599:Nitroprusside; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine
keywords: Acetylcholine; arterial pressure; current-induced vasodilation; endothelial dysfunction; iontophoresis; skin blood flow; sodium nitroprusside; sympathectomy; vascular reactivity