title: Effects of aging, TNF-α, and exercise training on angiotensin II-induced vasoconstriction of rat skeletal muscle arterioles.
abstract: 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.
authors.affiliation: Department of Health, Exercise and Sport Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Park
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Prisby
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Behnke
authors.forename: James M
authors.initials: JM
authors.lastname: Dominguez
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Judy
authors.initials: J
authors.lastname: Muller-Delp
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000502:physiology*; D004493:Education / Q000379:methods; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester