The rat cerebral vasculature exhibits time-of-day-dependent oscillations in circadian clock genes and vascular function that are attenuated following obstructive sleep apnea

Circadian clock components oscillate in cells of the cardiovascular system. Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and...

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Published in:Journal of cerebral blood flow and metabolism 2017-08, Vol.37 (8), p.2806-2819
Main Authors: Durgan, David J, Crossland, Randy F, Bryan, Robert M
Format: Article
Language:English
Subjects:
Animals
Cerebral Arteries - physiopathology
Cerebrovascular Disorders - etiology
Cerebrovascular Disorders - genetics
Cerebrovascular Disorders - physiopathology
Circadian Clocks - genetics
Circadian Clocks - physiology
Circadian Rhythm - genetics
Circadian Rhythm - physiology
Disease Models, Animal
Original
Period Circadian Proteins - genetics
Rats, Long-Evans
Sleep Apnea, Obstructive - complications
Sleep Apnea, Obstructive - genetics
Sleep Apnea, Obstructive - physiopathology
Vasodilation - physiology
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cited_by cdi_FETCH-LOGICAL-c434t-547d581dfb2daf1e52279ece5bd357a1e515fc8cfcac39ed4ecfadd3d9debf3
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container_title Journal of cerebral blood flow and metabolism
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creator Durgan, David J
Crossland, Randy F
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description Circadian clock components oscillate in cells of the cardiovascular system. Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and rhythms in vascular function. Apneas were produced in rats during sleep. Following two weeks of sham or obstructive sleep apnea, cerebral arteries were isolated over 24 h for mRNA and functional analysis. mRNA expression of clock genes exhibited 24-h rhythms in cerebral arteries of sham rats (p 
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Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and rhythms in vascular function. Apneas were produced in rats during sleep. Following two weeks of sham or obstructive sleep apnea, cerebral arteries were isolated over 24 h for mRNA and functional analysis. mRNA expression of clock genes exhibited 24-h rhythms in cerebral arteries of sham rats (p &lt; 0.05). Interestingly, peak expression of clock genes was significantly lower following obstructive sleep apnea (p &lt; 0.05). Obstructive sleep apnea did not alter clock genes in the heart, or rhythms in locomotor activity. Isolated posterior cerebral arteries from sham rats exhibited a diurnal rhythm in sensitivity to luminally applied ATP, being most responsive at the beginning of the active phase (p &lt; 0.05). This rhythm was absent in arteries from obstructive sleep apnea rats (p &lt; 0.05). Rhythms in ATP sensitivity in sham vessels were absent, and not different from obstructive sleep apnea, following treatment with L-NAME and indomethacin. We conclude that cerebral arteries possess a functional circadian clock and exhibit a diurnal rhythm in vasoreactivity to ATP. 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Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and rhythms in vascular function. Apneas were produced in rats during sleep. Following two weeks of sham or obstructive sleep apnea, cerebral arteries were isolated over 24 h for mRNA and functional analysis. mRNA expression of clock genes exhibited 24-h rhythms in cerebral arteries of sham rats (p &lt; 0.05). Interestingly, peak expression of clock genes was significantly lower following obstructive sleep apnea (p &lt; 0.05). Obstructive sleep apnea did not alter clock genes in the heart, or rhythms in locomotor activity. Isolated posterior cerebral arteries from sham rats exhibited a diurnal rhythm in sensitivity to luminally applied ATP, being most responsive at the beginning of the active phase (p &lt; 0.05). This rhythm was absent in arteries from obstructive sleep apnea rats (p &lt; 0.05). Rhythms in ATP sensitivity in sham vessels were absent, and not different from obstructive sleep apnea, following treatment with L-NAME and indomethacin. We conclude that cerebral arteries possess a functional circadian clock and exhibit a diurnal rhythm in vasoreactivity to ATP. 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subjects Animals
Cerebral Arteries - physiopathology
Cerebrovascular Disorders - etiology
Cerebrovascular Disorders - genetics
Cerebrovascular Disorders - physiopathology
Circadian Clocks - genetics
Circadian Clocks - physiology
Circadian Rhythm - genetics
Circadian Rhythm - physiology
Disease Models, Animal
Original
Period Circadian Proteins - genetics
Rats, Long-Evans
Sleep Apnea, Obstructive - complications
Sleep Apnea, Obstructive - genetics
Sleep Apnea, Obstructive - physiopathology
Vasodilation - physiology
title The rat cerebral vasculature exhibits time-of-day-dependent oscillations in circadian clock genes and vascular function that are attenuated following obstructive sleep apnea
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