Song-Young Park, Matthew J Rossman, Jayson R Gifford, Leena P Bharath, Johann Bauersachs, Russell S Richardson, E Dale Abel, J David Symons, Christian Riehle

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 weeks) 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 (RCR, 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 (CSA) and mitochondrial DNA content. Furthermore, compared to the SED mice, arteries from EX mice displayed elevated transcript levels of PGC-1α (Ppargc1a) and the downstream targets Cox4i1, Idh2, Idh3a, increased MnSOD protein expression, increased endothelial NO synthase (eNOS) phosphorylation (Ser1177), 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 to 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.