title: A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries.
abstract: Obstructive sleep apnea (OSA), a condition in which the upper airway collapses during sleep, is strongly associated with metabolic and cardiovascular diseases. Little is known how OSA affects the cerebral circulation. The goals of this study were 1) to develop a rat model of chronic OSA that involved apnea and 2) to test the hypothesis that 4 wk of apneas during the sleep cycle alters endothelium-mediated dilations in middle cerebral arteries (MCAs). An obstruction device, which was chronically implanted into the trachea of rats, inflated to obstruct the airway 30 times/h for 8 h during the sleep cycle. After 4 wk of apneas, MCAs were isolated, pressurized, and exposed to luminally applied ATP, an endothelial P2Y2 receptor agonist that dilates through endothelial-derived nitric oxide (NO) and endothelial-dependent hyperpolarization (EDH). Dilations to ATP were attenuated ~30% in MCAs from rats undergoing apneas compared with those from a sham control group (P < 0.04 group effect; n = 7 and 10, respectively). When the NO component of the dilation was blocked to isolate the EDH component, the response to ATP in MCAs from the sham and apnea groups was similar. This finding suggests that the attenuated dilation to ATP must occur through reduced NO. In summary, we have successfully developed a novel rat model for chronic OSA that incorporates apnea during the sleep cycle. Using this model, we demonstrate that endothelial dysfunction occurred by 4 wk of apnea, likely increasing the vulnerability of the brain to cerebrovascular related accidents.
authors.affiliation: Department of Anesthesiology, Baylor College of Medicine, Houston, Texas;
authors.forename: Randy F
authors.initials: RF
authors.lastname: Crossland
authors.forename: David J
authors.initials: DJ
authors.lastname: Durgan
authors.forename: Eric E
authors.initials: EE
authors.lastname: Lloyd
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Phillips
authors.forename: Anilkumar K
authors.initials: AK
authors.lastname: Reddy
authors.forename: Sean P
authors.initials: SP
authors.lastname: Marrelli
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bryan
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012119:Respiration; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014132:Trachea / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D020030:Nitric Oxide Donors; D058912:Purinergic P2Y Receptor Agonists; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
keywords: cerebrovascular circulation; endothelial dysfunction; hypoxia/reoxygenation; obstructive sleep apnea; sleep-disordered breathing