title: Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles.
abstract: Exercise training ameliorates age-related impairments in endothelium-dependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise training-induced enhancement of endothelial function occurs, in part, through an increase in ROS signaling.
authors.affiliation: Department of Physiology and Pharmacology, and the Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.forename: Rafael
authors.initials: R
authors.lastname: Reyes
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Payal
authors.initials: P
authors.lastname: Ghosh
authors.forename: Alvaro N
authors.initials: AN
authors.lastname: Gurovich
authors.forename: Lori S
authors.initials: LS
authors.lastname: Kang
authors.forename: Arturo J
authors.initials: AJ
authors.lastname: Cardounel
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
authors.forename: Judy M
authors.initials: JM
authors.lastname: Muller-Delp
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013663:Teaching; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D003497:Cyclic N-Oxides; D045462:Endothelium-Dependent Relaxing Factors; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases; D000109:Acetylcholine; C001803:tempol; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat