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Impaired myogenic tone in overweight rats exposed to simulated sleep apnea is due to elevated iNOS‐derived nitric oxide
Author(s) -
Sweazea Karen L.,
Kanagy Nancy L.,
Walker Benjimen R.
Publication year - 2008
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.22.1_supplement.732.4
Subject(s) - endocrinology , medicine , nitric oxide , intermittent hypoxia , nitric oxide synthase , blood pressure , chemistry , obstructive sleep apnea , mesenteric arteries , sleep apnea , artery
Exposure of rats to eucapnic intermittent hypoxia (E‐IH) results in vascular abnormalities similar to those seen in humans with sleep apnea. However, sleep apnea is often associated with increased adiposity. Therefore, we examined the potential interaction between these factors. Since increased adiposity may be associated with elevated expression of inducible nitric oxide synthase (iNOS), we hypothesized that overweight rats would not exhibit enhanced myogenic tone following exposure to simulated sleep apnea. Rats were fed either chow or a high fat diet (HFD; 60% kcal from fat) for 6 weeks. During the final 14 days of each diet, animals were exposed to either air or E‐IH. Both Chow E‐IH and HFD Air rats developed increased systolic blood pressure, whereas HFD E‐IH rats were less hypertensive and had elevated plasma nitric oxides. Consistent with our hypothesis, myogenic tone in response to increasing intraluminal pressure was attenuated in isolated mesenteric arterioles from both HFD Air and HFD E‐IH rats compared to Chow Air controls. Inhibition of iNOS with L‐N 6 ‐(1‐Iminoethyl) lysine hydrochloride (L‐NIL, 10 μM) restored myogenic reactivity in these arteries to the level of Chow Air rats. Despite normalization of myogenic reactivity, L‐NIL did not restore the diminished pressure‐induced increase in vascular smooth muscle (VSM) calcium to Chow Air levels. These results suggest that HFD‐induced elevation in iNOS‐derived NO impairs myogenic tone in both HFD Air and HFD E‐IH arteries by diminishing VSM calcium sensitivity.