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Uncoupling of Oxidative Phosphorylation in Vascular Function in Aging.
Author(s) -
Mendoza Suelhem Alejandra,
Chilian William M,
Brzezinska Anna K
Publication year - 2007
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.21.6.a902-b
Subject(s) - oxidative phosphorylation , oxidative stress , medicine , endocrinology , isometric exercise , acetylcholine , uncoupling protein , mitochondrion , chemistry , reactive oxygen species , endothelium , vasodilation , mitochondrial ros , biology , biochemistry , brown adipose tissue , obesity
Aging is a risk factor for the development of CVD and is characterized by a reduced vascular reactivity and increased free radical generation (ROS). The uncoupling of oxidative phosphorylation (OXPHOS) reduces ROS generation. We hypothesized that endothelium‐dependent (EDD) and endothelium‐independent (EIND) dilation is linked to mitochondrial uncoupling. Isometric tension experiments were performed in Fisher 344 (F344, 15–16 months) rat aortic rings. Acetylcholine (Ach, 10 μM, n=13 rings) caused 10% vasodilation (n= 19). The EIND dilation was tested with MAHMA NONO‐ate (10μM) and rings responded with 46% (n= 13, P<0.05) relaxation. FCCP (1 μM) a chemical uncoupler of OXPHOS had no effects on neither EDD nor EIND (n=6, ns). Bay 41–2272 (10 μM), stimulator of soluble guanylate cyclase (sGC) improved relaxation to Ach, and arteries responded with 56% (n=6, P<0.05) relaxation; relaxation to MAHMA was at 71% (n=6, P<0.05). The expression of uncoupling protein UCP‐2 in heart and aorta of F344 was increased by 30% (3 hearts, 3 aortas, n=2), respectively; the expression of UCP‐3 was increased by 3‐fold (n=3) in F344 hearts as compare to age matched controls. Taken together, a decline in vascular function is consistent with progressive oxidative stress. The oxidative modification of proteins could be responsible for a lack of activation of a negative feedback via the uncoupling of OXPHOS and reduction in ROS levels.