Document Detail

Effects of aging, TNF-α, and exercise training on angiotensin II-induced vasoconstriction of rat skeletal muscle arterioles.
MedLine Citation:
PMID:  22923503     Owner:  NLM     Status:  MEDLINE    
Skeletal muscle vascular resistance during physical exertion is higher with old age. The purpose of this study was to determine whether 1) aging enhances angiotensin II (ANG II)-induced vasoconstriction; 2) the proinflammatory cytokine tumor necrosis factor (TNF)-α contributes to alterations in ANG II-mediated vasoconstriction with aging; 3) exercise training attenuates putative age-associated increases in ANG II-mediated vasoconstriction; and 4) the mechanism(s) through which aging and exercise training alters ANG II-induced vasoconstriction in skeletal muscle arterioles. Male Fischer 344 rats were assigned to four groups: young sedentary (4 mo), old sedentary (24 mo), young trained, and old trained. In a separate group of young sedentary and old sedentary animals, a TNF type 1 receptor inhibitor was administered subcutaneously for 10 wk. First-order arterioles were isolated from soleus and gastrocnemius muscles for in vitro experimentation. Old age augmented ANG II-induced vasoconstriction in both soleus (young: 27 ± 3%; old: 38 ± 4%) and gastrocnemius (young: 42 ± 6%; old: 64 ± 9%) muscle arterioles; this augmented vasoconstriction was abolished with the removal of the endothelium, N(G)-nitro-l-arginine methyl ester, and chronic inhibition of TNF-α. In addition, exercise training ameliorated the age-induced increase in ANG II vasoconstriction. These findings demonstrate that old age enhances and exercise training diminishes ANG II-induced vasoconstrictor responses in skeletal muscle arterioles through an endothelium-dependent nitric oxide synthase signaling pathway. In addition, the enhancement of ANG II vasoconstriction with old age appears to be related to a proinflammatory state.
Yoonjung Park; Rhonda D Prisby; Brad J Behnke; James M Dominguez; Lisa A Lesniewski; Anthony J Donato; Judy Muller-Delp; Michael D Delp
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-08-23
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  113     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-05-23     Revised Date:  2013-10-10    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1091-100     Citation Subset:  IM    
Department of Health, Exercise and Sport Sciences, Texas Tech University, Lubbock, TX, USA.
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MeSH Terms
Aging / metabolism,  physiology*
Angiotensin II / metabolism*
Arterioles / metabolism,  physiology*
Education / methods
Endothelium, Vascular / metabolism,  physiology*
Muscle, Skeletal / blood supply*,  metabolism
NG-Nitroarginine Methyl Ester / metabolism
Nitric Oxide Synthase / metabolism
Physical Conditioning, Animal
Rats, Inbred F344
Tumor Necrosis Factor-alpha / antagonists & inhibitors,  metabolism*
Vascular Resistance / physiology
Vasoconstriction / physiology*
Grant Support
K01 AG031327-01/AG/NIA NIH HHS
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; 11128-99-7/Angiotensin II; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Oxide Synthase

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