Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Abstract

Sindler AL, Reyes R, Chen B, Ghosh P, Gurovich AN, Kang LS, Cardounel AJ, Delp MD, Muller-Delp JM. Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles. J Appl Physiol 114: [681][682][683][684][685][686][687][688][689][690][691][692][693] 2013. First published January 3, 2013; doi:10.1152/japplphysiol.00341.2012.-Exercise training ameliorates age-related impairments in endotheliumdependent 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 traininginduced enhancement of endothelial function occurs, in part, through an increase in ROS signaling. hydrogen peroxide; superoxide; peroxynitrite; nitric oxide; acetylcholine ENDOTHELIAL FUNCTION IN THE skeletal muscle resistance vasculature declines with age primarily due to decreased nitric oxide (NO) bioavailability (10,38,51,55). In feed arteries from soleus muscle, reductions in NO-dependent vasodilation are accompanied by reduced expression of endothelial NO synthase (eNOS) (65). In contrast, our laboratory has previously reported that NO-mediated vasodilation of soleus muscle arterioles declines with advancing age, despite an increase in eNOS protein levels (51). Thus the age-related decline in bioavailability of NO may be dependent on numerous other factors that regulate both NO production and degradation. eNOS activity, and subsequent NO production, is regulated by availability of substrate and cofactors, by protein-...

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

“…Similar to previous studies, we find that scavenging superoxide improves EDD in conduit and cerebral arteries from old mice (Blackwell et al 2004;Lesniewski et al 2009;Mayhan et al 2008;Modrick et al 2009) and does not affect EDD in conduit arteries from young or old CR mice (Csiszar et al 2009). However, we demonstrate that scavenging superoxide in the MCA from young and old CR mice results in reduced EDD, which is in accordance with previous studies demonstrating reactive oxygen species contribute to the dilation of resistance arteries in skeletal muscle (Sindler et al 2013;Trott et al 2011), cardiac muscle (Miura et al 2003;Feng et al 2010;Kang et al 2011), and cerebral tissue (Drouin et al 2007). Similarly, brachial artery dilation to handgrip exercise in humans, which is NO-dependent (Wray et al 2011), is improved in older adults following ingestion of an antioxidant cocktail, but is reduced in young adults after the same antioxidant cocktail .…”

“…In contrast, inhibiting NADPH oxidase impairs EDD in the MCAs from young mice and old CR mice. Inhibition of NADPH oxidase also impairs EDD in skeletal muscle arterioles of young mice (Sindler et al 2013;Trott et al 2011). These results indicate that reactive oxygen species produced by NADPH oxidase impair EDD with aging, but contribute to functional resistance artery EDD in young and lifelong CR mice.…”

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