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Reversal of Age‐related Impairment in Collateral Growth by Tempol
Author(s) -
Coppinger Brian,
Theodorakis Janice L,
Theodorakis Nicholas G,
Pride P Melanie,
Unthank Joseph L,
Miller Steven J
Publication year - 2006
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.20.5.a1085-b
Subject(s) - medicine , endocrinology , ligation , nitric oxide , collateral circulation , collateral damage , pathogenesis , tetrahydrobiopterin , antioxidant , chemistry , nitric oxide synthase , biochemistry , psychology , criminology
Objective We have previously shown that collateral growth is impaired with both aging and hypertension, and that tempol restored collateral growth in hypertensive rats. The aim of this study was to determine if antioxidant therapy could reverse the age‐related impairment of collateral growth and if nitric oxide (NO) was required. Methods Young (~200g) and old (>600g) male Wistar rats were used in these studies. Old rats were given either tempol (53 mg/kg/day, drinking water), tempol plus L‐NAME (1.6 mg/kg/day) or regular drinking water. Ileal arteries were induced to become collaterals via ligation of adjacent arteries. Collateral growth (% luminal expansion) was measured 7 days after ligation. Total RNA was isolated from control arteries and mRNA expression analyzed using real‐time PCR. Plasma tetrahydrobiopterin (BH 4 ) was measured using HPLC. Results As previously described, collateral development was inhibited with aging (33.0±4.3% young vs. 2.1±6.7% old; p<0.05). Treatment with the SOD mimetic tempol partially restored the capacity for collateral growth in old rats (17.6±5.8%, p=0.03). This increase was abolished when rats were administered tempol plus L‐NAME. p22 phox mRNA was increased 1.54±0.2 fold (p=0.03) in control vessels of old vs. young rats. Plasma BH 4 was significantly decreased in old vs. young rats (0.073±0.009 vs. 0.122±0.013 uM; p=0.03), consistent with an age‐related increase in systemic oxidant stress. Conclusion The data are consistent with the hypothesis that an imbalance in superoxide and NO bioavailability mediates the age‐related impairment of collateral growth. Support: HL 42898