Exercise training improves vascular mitochondrial function

Abstract

Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-γ coactivator-1α and the downstream targets cytochrome c oxidase subunit IV isoform 1,isocitrate dehydrogenase(Idh)2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser(1177)), and suppressed reactive oxygen species generation (all P< 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function.

Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice

“…However, in contrast to some previous reports investigating the effects of exercise on arterial mitochondria [27–28, 40–42] we did not observe an increase in arterial mitochondrial respiratory protein content with voluntary aerobic exercise. The lack of increase in mitochondrial protein content that we observed may be attributable to the nature of the exercise intervention, as voluntary wheel running—an intermittent stimulus—is distinctly different than the forced, continuous treadmill and swimming exercise paradigms employed in previous investigations.…”

“…However, given that vascular mitochondria are particularly critical for intra- and inter- cellular signaling functions [10–12], mitochondria in both vascular cell types are likely important for regulation of arterial endothelial function. In addition to our finding that preserved arterial resilience with exercise is accompanied by improvements in whole artery mitochondrial health, previous work has also demonstrated that alterations in whole artery and VSMC mitochondrial health with aging, disease and exercise are accompanied by corresponding changes in endothelial function [13–14, 27–28, 40–42]. …”

“…It is well known that aerobic exercise improves mitochondrial biogenesis and homeostasis in non-vascular tissues [34–39], and recent work suggests that exercise can also improve markers of arterial mitochondrial content and health in healthy animals [27–28, 40–42], but the effects of aerobic exercise on arterial mitochondria with primary aging are unclear. We tested the hypothesis that aging would be associated with impaired arterial resilience to acute stress and reduced arterial mitochondrial health in mice, and that voluntary aerobic exercise initiated in late-life (10 weeks of voluntary wheel running) would increase resilience and improve mitochondrial health in aging arteries.…”

Exercise improves high fat diet-impaired vascular function

“…The qPCR data were obtained from five different samples in triplicate. Calculations of relative normalized gene expression were performed according to the ΔCt method as described before (7). The data were normalized to housekeeping gene, 18S ribosomal RNA.…”

“…The combination of abnormal eating habits and a sedentary lifestyle increase the risk factors of obesity and CVD (6). A previous study has demonstrated that exercise improves vascular function by increasing the vascular mitochondrial respiratory capacity, bioavailable nitric oxide (NO), and redox balance in a sedentary rodent model (7). While prolonged sitting in humans prompts leg endothelial dysfunction, fidgeting improves leg endothelial and vascular function through the intermittent increases in vascular shear stress (8).…”