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Effects of chronic intermittent hypoxia on endothelial function in mice
Author(s) -
Miller Jordan Daniel,
Lund Donald D,
Heistad Donald D
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1165-c
Subject(s) - sodium nitroprusside , superoxide , hypoxia (environmental) , medicine , aorta , dilator , endocrinology , intermittent hypoxia , nitric oxide , lucigenin , acetylcholine , endothelial dysfunction , vasodilation , chemistry , oxygen , obstructive sleep apnea , biochemistry , organic chemistry , enzyme
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/mm 2 in CTRL animals to 28 ± 16 RLU/sec/mm 2 in CIH mice. The superoxide scavenger, Tiron, eliminated these differences in chemiluminescence in aorta (CTRL = 1 ± 3 RLU/sec/mm 2 , CIH = 1 ± 5 RLU/sec/mm 2 ). 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.