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.