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Anti‐inflammatory treatment restores endothelium‐dependent dilation in older mice by increasing nitric oxide bioavailability
Author(s) -
Connell Melanie L,
Durrant Jessica R,
Folian Brian J,
Russell Molly J,
Seals Douglas R,
Lesniewski Lisa A
Publication year - 2008
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.22.1_supplement.967.5
Subject(s) - dilator , sodium nitroprusside , nitric oxide , vasodilation , endothelium , endocrinology , medicine , endothelial dysfunction , nitric oxide synthase , chemistry , inflammation , diclofenac sodium , pharmacology
Chronic low‐grade inflammation may contribute to impaired endothelium‐dependent dilation (EDD) with aging, but evidence is limited. To gain further insight, we studied isolated carotid arteries from young (Y, 4–7 mo) and older (O, 29–34 mo) B6D2F1 mice (n=6–8/group). Maximal carotid artery dilation to acetylcholine (ACh), an endothelium‐dependent dilator, was 24% lower in O (76±3 vs. 99±1%, mean±SE, P=0.001). Administration of the nitric oxide (NO) synthase inhibitor N G ‐nitro‐L arginine methyl ester (L‐NAME) decreased ACh dilation less (P=0.02) in O (−20% to 56±8%) vs. Y (−51% to 48±8%). Treatment with the anti‐inflammatory compound sodium salicylate (200 mg/kg/d via diet for 5 d, n=5/group) resulted in similar ACh dilation (P=0.98) in O and Y mice before (O: 97±2 vs. Y: 99±1%) and after (O: 45±15 vs. Y: 43±9%) L‐NAME. Inhibition of superoxide with TEMPOL markedly improved EDD in untreated, but not in sodium salicylate treated O mice or in Y mice. Carotid artery dilation to the endothelium‐independent dilator sodium nitroprusside was not different in Y and O and was not affected by sodium salicylate (P=0.93). These preliminary results support the hypothesis that the development of vascular inflammation plays a key role in impaired EDD with aging in B6D2F1 mice through an oxidative stress‐mediated reduction in NO bioavailability. Supported by NIH AG006537, AG013038 and AG022241