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Am J Physiol Regul Integr Comp Physiol. 2013 Aug 15;305(4):R334-42. doi: 10.1152/ajpregu.00244.2013. Epub 2013 Jun 12.

A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries.

Author information

1
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas;

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.

KEYWORDS:

cerebrovascular circulation; endothelial dysfunction; hypoxia/reoxygenation; obstructive sleep apnea; sleep-disordered breathing

PMID:
23761641
PMCID:
PMC3833398
DOI:
10.1152/ajpregu.00244.2013
[Indexed for MEDLINE]
Free PMC Article

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