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Sodium nitrite treatment restores vascular endothelial function in old mice with CKD
Author(s) -
Sindler Amy L,
Zigler Melanie C,
Yoshizawa Mutsuko,
Baylis Chris,
Seals Douglas R
Publication year - 2012
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.26.1_supplement.865.17
Subject(s) - nitrite , endothelial dysfunction , oxidative stress , medicine , renal function , endocrinology , sodium nitrite , vasodilation , endothelium , superoxide dismutase , superoxide , bioavailability , chemistry , pharmacology , biochemistry , food science , organic chemistry , nitrate , enzyme
We tested the hypothesis that sodium nitrite treatment would improve endothelial function in older mice with chronic kidney disease (CKD). Old (~27 mo) C57 male mice that underwent 5/6 nephrectomy (OCKD, n=4) had greater circulating plasma creatinine vs. old control (O, n=5) (0.067 ± 0.03 vs. 0.017 ± 0.002 mg/dl, p ≤ 0.01). Endothelium‐dependent dilation (EDD) (carotid artery dilation to acetylcholine [ACh]) was impaired in O vs. young (~6 mo, Y, n=4) (80 ± 1 vs. 96 ± 3%, p < 0.05), and was impaired further with CKD (71 ± 2%), which was mediated by reduced NO (EDD to ACh alone minus EDD to ACh + L‐NAME: Y 62 ± 9% vs. O 43 ± 2% vs. OCKD 32 ± 6%, p < 0.05). Sodium nitrite added to drinking water (50 mg/l) for 8 weeks completely restored EDD in OCKD (92 ± 4%) by restoring NO bioavailability (61 ± 19%). Incubation with the superoxide dismutase mimetic, TEMPOL, increased EDD in O and OCKD (96 ± 1 and 95 ± 3%), but had no effect in Y or OCKD mice treated with nitrite. Endothelium‐independent dilation did not differ among groups/conditions. Superoxide production (EPR spectroscopy) from aortic rings was greater in O vs. Y (4139 ± 406 vs. 1734 ± 368 AU), further increased in OCKD (5858 ± 1509 AU), and normalized by sodium nitrite treatment (2697 ± 265 AU). These results indicate that nitrite supplementation may be an effective therapy for enhancing vascular endothelial function in age‐associated CKD by improving NO bioavailability and oxidative stress. Work supported by NIH AG013038, HL007822, AG000279