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Tempol normalizes aortic relaxation but not elevated isoprostanes or PGE2 in copper‐deficient rats
Author(s) -
Schuschke Dale,
Johnson W. Thomas,
Adeagbo Ayotunde
Publication year - 2009
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.23.1_supplement.727.3
Subject(s) - oxidative stress , chemistry , endocrinology , nitric oxide , medicine , reactive oxygen species , copper deficiency , isoprostanes , copper , inflammation , antioxidant , isoprostane , weanling , lipid peroxidation , biochemistry , organic chemistry
Copper deficiency promotes accumulation of reactive oxygen species, which likely impair nitric oxide (NO)‐ mediated relaxation as well as trigger vascular inflammation. We hypothesize that an antioxidant supplementation would diminish oxidative stress, restore aortic relaxation, and limit pro‐inflammatory prostaglandin E 2 (PGE 2 ) synthesis during Cu deficiency. Weanling male Sprague Dawley rats were fed purified diets which were either copper‐adequate (Cu‐A; 6.3 μg Cu/g diet); copper‐deficient (Cu‐D; 0.3 μg Cu/g diet), or the Cu‐D diet combined with the SOD mimetic Tempol (Cu‐D/T; 1mM in drinking water) for 4 weeks. Relaxation of aortic rings was measured with force displacement transducers coupled to a Grass polygraph. Acetylcholine‐induced NO‐mediated relaxation was significantly less in the Cu‐D (pD 2 = 6.77 ± 0.10) vs Cu‐A (pD 2 = 8.18 ± 0.30); the decrease was normalized in Cu‐D/Tempol (pD 2 = 7.75 ± 0.16) rats. Serum isoprostanes (index of oxidative stress) and PGE 2 were higher in both the Cu‐D and Cu‐D/T groups vs Cu‐A controls. Thus, Cu‐deficency significantly impaired NO‐mediated relaxation and tempol supplementation restored aortic responsiveness. Our data also suggest a role for copper as a modulator of oxidative stress and inflammation independent of SOD activity or NO‐derived oxidants. Support: NIH DK055030.