Obstructive Sleep Apnea Attenuates the Cerebrovascular Circadian Clock and Rhythms in Vascular Function

Abstract

Molecular circadian clock components oscillate in cells of the cardiovascular system. These clocks allow the cell to respond to a stimulus with proper timing and magnitude. Alterations in these rhythms are associated with and/or contribute to various cardiovascular diseases. We tested the hypothesis that obstructive sleep apnea (OSA) disrupts the normal rhythms of the cerebrovascular circadian clock and vascular function. OSA was produced in rats by remotely inflating a balloon placed in the trachea. Unanesthetized rats underwent 60 apneas/ hour for 8 hours/ day (sleep phase). Following 2 weeks of sham or OSA, cerebral arteries were isolated at; the transition from dark‐to‐light (i.e., zeitgeber time (ZT) 0), 6, 12, or 18. We identified significant diurnal rhythms in mRNA expression levels of the circadian clock genes period 1 (per1), period 2 (per2), and the clock controlled gene albumin d‐site binding protein (dbp) in cerebral vessels of sham rats, which were significantly attenuated following OSA (p<0.05 for each). Perfused posterior cerebral arteries from sham rats exhibit a significant diurnal rhythm in the sensitivity to ATP induced vasodilation, that was most responsive at the beginning of the awake phase (p<0.05). This rhythm was abolished in OSA arteries, which exhibit diminished ATP sensitivity independent of the time‐of‐day (p<0.05). In the presence of L‐NAME the diurnal rhythm in ATP sensitivity was abolished in sham vessels and not different from OSA, suggesting cerebral arteries exhibit a diurnal rhythm in nitric oxide induced vasodilation that is impaired following OSA. In conclusion, OSA significantly attenuates the diurnal rhythms of the cerebrovascular circadian clock and vascular function. Funded by 1R01NS080531