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Aging impairs flow‐induced dilation in skeletal muscle feed arteries: role of Akt‐dependent phosphorylation of eNOS
Author(s) -
Luttrell Meredith,
Seawright John,
Trott Daniel,
Woodman Christopher
Publication year - 2012
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.26.1_supplement.lb636
Subject(s) - enos , protein kinase b , phosphorylation , dilator , medicine , endocrinology , pi3k/akt/mtor pathway , snap , nitric oxide , chemistry , nitric oxide synthase , biochemistry , signal transduction , computer graphics (images) , computer science
We tested the hypothesis that impaired nitric oxide (NO)‐mediated, endothelium‐dependent dilation in aged soleus muscle feed arteries (SFA) is due to an age‐related decrement in PI3K/Akt‐dependent phosphorylation of endothelial NO synthase (eNOS) on serine 1177 (p‐eNOS ser1177 ). SFA from young and old Fischer 344 rats were cannulated for examination of flow‐induced dilation (FID). To determine how aging affected FID, dilator responses were assessed in the absence and presence of pharmacological inhibitors of NOS (L‐NNA), PI3K (LY‐294002), or Akt (AktI). Results indicate that FID was blunted in old SFA, while dilation to sodium nitroprusside was not compromised. Age‐group differences in FID were abolished in the presence of L‐NNA, LY‐294002, or AktI. In a separate experiment, FID was assessed in SFA from young and old rats. After FID assessment, SFA were then removed from the pipettes, snap frozen, and immunoblot analysis was used to assess p‐Akt Ser473 , p‐eNOS ser1177 , total Akt and total eNOS protein content. FID was blunted in old SFA; however, the p‐Akt Ser473 /Akt and p‐eNOS ser1177 /eNOS ratios were similar in young and old SFA. Collectively, these results indicate that NO‐mediated dilation is impaired in old SFA, but is not due to reduced PI3K/Akt‐dependent phosphorylation of eNOS. Research supported by AHA 0765043 and AHA 4150031 (CRW), and Sydney and J. L. Huffines Institute of Sports Medicine Graduate Student Research Grants (MJL, JWS, and DWT).