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Vascular effects of Nox2‐derived radicals are dependent upon mitochondrial antioxidant capacity in old mice
Author(s) -
Roos Carolyn M,
Hagler Michael A,
Arghami Arman,
Miller Jordan D
Publication year - 2011
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.25.1_supplement.1093.7
Subject(s) - apocynin , reactive oxygen species , mitochondrial ros , endocrinology , nadph oxidase , medicine , endothelial dysfunction , antioxidant , acetylcholine , oxidative stress , mitochondrion , chemistry , biology , biochemistry
Reactive oxygen species (ROS)‐induced ROS release occurs when increased mitochondrial ROS generation increases NAD(P)H oxidase activity, and vice‐versa. Whether this phenomenon contributes to age‐related endothelial dysfunction is unknown. We tested the hypothesis that reductions in mitochondrial antioxidant capacity worsen endothelial function in old mice through augmented ROS‐induced ROS release. Endothelial function and gene expression were examined in aorta from young (2 mo) and old (>18 mo) male MnSOD wild‐type (WT) and MnSOD‐deficient (HET) mice. Maximum relaxation to acetylcholine (M R, ACH ) was unaffected in young HET mice (44 ± 3%) compared to WT mice (39% ± 3). Aging significantly impaired M R, ACH in WT mice (55 ± 3%), though M R, ACH did not differ between old WT and old HET mice (54% ± 3). Incubation with apocynin did not affect M R, ACH in young mice, but improved M R, ACH in old WT mice (43%± 3). Surprisingly, apocynin significantly impaired M R, ACH in old HET mice (60% ± 5). Expression of Nox2 was significantly increased in old mice, but unaffected by genotype. In conclusion, Nox2‐derived ROS contribute to endothelial dysfunction in old mice with intact mitochondrial antioxidant defenses. Loss of mitochondrial antioxidant capacity with aging, however, appears to activate a Nox2‐dependent, ROS‐induced ROS‐release cycle that paradoxically protects against endothelial dysfunction in old mice. NHLBI