Aging impairs PI3K/Akt signaling and NO-mediated dilation in soleus muscle feed arteries.
Eur J Appl Physiol
; 113(8): 2039-46, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23563601
ABSTRACT
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 decline in the potential for PI3-kinase (PI3K)/protein kinase B (Akt)-dependent phosphorylation of endothelial NO synthase (eNOS) on serine residue 1177 (p-eNOS(ser1177)). SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism by which aging affected vasodilation to flow and ACh, vasodilator responses were assessed in the presence of N (ω)-nitro-L-arginine (L-NNA, to inhibit NOS), LY-294002 (to inhibit PI3K), or 1L6-hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate (AktI, to inhibit Akt). Flow- and ACh-induced vasodilator responses were significantly impaired in old SFA, whereas endothelium-independent dilation to SNP was not compromised. Age-group differences in flow- and ACh-induced dilations were abolished in the presence of L-NNA, LY-294002, or AktI. In a separate experiment, SFA were cannulated and stimulated with ACh (10(-4) M, 3 min), flow (60 µl/min, 5 min), or remained unstimulated (3 min). SFA were removed from the pipettes and immunoblot analysis was used to assess ACh- and flow-stimulated phosphorylation of eNOS on ser(1177). Stimulation with ACh or flow increased phosphorylation of eNOS on ser(1177) in young (not old) SFA. Preincubation of young SFA with LY-294002, abolished the ACh-induced phosphorylation of eNOS in young SFA. Collectively, these results indicate that impaired NO-mediated, endothelium-dependent dilation in old SFA is due, in part, to an impaired potential for PI3K/Akt-dependent phosphorylation of eNOS on ser(1177).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
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Envelhecimento
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Endotélio Vascular
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Músculo Esquelético
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Eur J Appl Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos