High‐intensity interval training prevents oxidantmediated diaphragm muscle weakness in hypertensive mice

Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)‐salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high‐intensity interval training (HIIT). Sham‐treated ( n = 11), DOCA‐salt‐treated ( n = 11), and DOCA‐salt+HIIT‐treated ( n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross‐sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA‐salt mice independent of HIIT ( P < 0.05). Diaphragm forces were impaired by ~15–20% in DOCA‐salt vs . sham‐treated mice ( P < 0.05), but this effect was prevented after HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (~30%; P = 0.06) in DOCA‐salt vs . sham‐ and DOCA‐salt+HIIT mice, whereas oxidative stress increased ( P < 0.05). Enzyme activity of NADPH oxidase was higher, but superoxide dismutase was lower, with MyHC oxidation elevated by ~50%. HIIT further prevented direct oxidant‐mediated diaphragmcontractile dysfunction ( P < 0.05) after a 30 min exposure to H 2 O 2 (1 mM). Our data suggest that hypertension induces diaphragm contractile dysfunction via an oxidantmediated mechanism that is prevented by HIIT.—Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High‐intensity interval training prevents oxidantmediated diaphragm muscle weakness in hypertensive mice. FASEB J. 31, 60–71 (2017) www.fasebj.org