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Age‐related impairment in collateral growth is due to oxidant stress and decreased nitric oxide bioavailability
Author(s) -
Madren Kathryn,
Bratz Ian,
Dick Gregory,
Tune Johnathan,
Bohlen H. Glenn,
Pride P. Melanie,
Bills Randall,
Zhou Xiaosun,
Unthank Joseph,
Miller Steven J
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.a1213-d
Subject(s) - apocynin , nad(p)h oxidase , nitric oxide , medicine , endocrinology , oxidative stress , nadph oxidase , chemistry , superoxide , nad+ kinase , superoxide dismutase , enzyme , biochemistry
Previous results demonstrated that collateral growth (CG) is impaired with aging and that partial reversal of the impairment by tempol was nitric oxide (NO)‐dependent. The aim of this study was to determine the source of oxidant stress and the relationship between increased shear and NO production during aging. Plasma glutathione reduced/oxidized ratio as measured by the enzymatic recycling method was 0.76±0.23 vs. 0.074±0.066 (p=0.02) in young (200g) and aged (>600g) Wistar male rats, respectively, consistent with an age‐related increase in systemic oxidant stress. Aged rats were given either the NAD(P)H oxidase inhibitor apocynin or regular drinking water, and ileal arteries were induced to become collaterals via ligation of adjacent arteries. CG (% luminal expansion) measured 7 days after ligation showed that treatment with apocynin increased CG capacity in old rats (18.3±2.2% vs. control, 3.0±0.6%; p=0.03). Acetylcholine‐induced relaxation as determined with isolated vessels was significantly decreased in aged rats, but enhanced by acute treatment with tempol or apocynin. Aged rats demonstrated a total lack of shear‐mediated increased NO concentrations at both low and high flow levels (p<0.05 vs. young) as measured by NO‐specific electrodes. The data are consistent with the hypothesis that an imbalance in NAD(P)H oxidase‐derived superoxide and NO mediates the age‐related impairment of CG. Support: HL 42898