Effects of chronic intermittent hypoxia on endothelial function in mice

Abstract

Sleep apnea in humans is characterized by intermittent severe hypoxia, and is associated with endothelial dysfunction. We examined effects of intermittent severe hypoxia on endothelial function in C57BL/6J mice. Chronic intermittent hypoxia (CIH = 60 second cycles, nadir fraction of inspired oxygen = 0.05, n = 4) or comparable intermittent bursts of room air (CTRL, n = 4) was administered in a plexiglass chamber for 12 hours per day for 15–22 days. Responses to acetylcholine and nitroprusside were examined in aortic and carotid arterial rings. Maximal relaxation in response to acetylcholine in aorta was reduced from 82 ± 4% (mean ± SE) in CTRL mice to 71 ± 8% in the CIH mice. In carotid arteries, maximal relaxation in response to acetylcholine was reduced from 89 ± 6% in CTRL mice to 66 ± 8% in CIH mice. Vascular relaxation in response to sodium nitroprusside was unaltered by CIH in both aorta (CTRL = 97 ± 2, CIH = 96 ± 2) and carotid rings (CTRL = 98 ± 1%, CIH = 93 ± 3%). Vascular superoxide (lucigenin) in the aorta increased from 15 ± 13 RLU/sec/mm2 in CTRL animals to 28 ± 16 RLU/sec/mm2 in CIH mice. The superoxide scavenger, Tiron, eliminated these differences in chemiluminescence in aorta (CTRL = 1 ± 3 RLU/sec/mm2, CIH = 1 ± 5 RLU/sec/mm2). These data suggest that CIH impairs endothelial function in mice, perhaps as a result of increased superoxide and reduction in nitric oxide bioavailability. This experimental model in mice may be useful for elucidation of mechanisms that contribute to vascular dysfunction with CIH.