Abstract 106: Chronic Intermittent Hypoxia Induces Neurovascular Dysfunction through Endothelin-1 and Nox2-Derived Radical

Obstructive sleep apnea (OSA), a condition resulting in chronic intermittent hypoxia (CIH), is an independent risk factor for ischemic stroke, but the mechanisms of the effect are unknown. We hypothesized that CIH increases stroke risk by altering the regulation of cerebral blood flow (CBF) and increasing the brain’s susceptibility to ischemia. Male C57Bl/6 mice (n=5/group) were subjected to CIH (10% O 2 for 90 sec/room air for 90 sec; during sleep hours) for 14 or 35 days (d). Sham-treated mice received room air according to the same schedule. Somatosensory cortex CBF was assessed by laser-Doppler flowmetry in anesthetized mice equipped with a cranial window. CIH increased mean arterial pressure only at 35d (from 74±2 to 83±3 mmHg (p and by whisker stimulation (sham: 23±1%;CIH: 14±1%;p 0.05), indicating that smooth muscle relaxation was not compromised. The effects of CIH were prevented by neocortical application of the endothelin (ET) type A (ET A ) receptor antagonist BQ123 (1µM;p 0.05). CIH increased reactive oxygen species (ROS) by 2.3±0.5 folds (p