High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice

• Published in: The FASEB journal 2017-01, Vol.31 (1), p.60-71
• Main Authors: Bowen, T Scott, Eisenkolb, Sophia, Drobner, Juliane, Fischer, Tina, Werner, Sarah, Linke, Axel, Mangner, Norman, Schuler, Gerhard, Adams, Volker
• Format: Article
• Language: English
• Subjects: Acetic acid; Animals; Blood pressure; Cardiovascular Physiological Phenomena; Desoxycorticosterone - administration & dosage; Desoxycorticosterone - pharmacology; Diaphragm; Diaphragm (anatomy); Diaphragm - pathology; Enzymatic activity; Enzyme activity; Enzymes; Heart; Heart diseases; High-Intensity Interval Training; Hypertension; Male; Mice; Mice, Inbred C57BL; Mineralocorticoids - administration & dosage; Mineralocorticoids - pharmacology; Mitochondria - physiology; Muscle contraction; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Weakness - metabolism; Muscle Weakness - prevention & control; Muscles; Myosin; NAD(P)H oxidase; Oxidants - metabolism; Oxidation; Oxidative Stress; Physical Conditioning, Animal - physiology; Protein expression; Risk factors; Rodents; Salts; Superoxide dismutase; Training
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201600672R

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 diaphragm contractile dysfunction (P < 0.05) after a 30 min exposure to H O- (1 mM). Our data suggest that hypertension induces diaphragm contractile dysfunction via an oxidant-mediated 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 oxidant-mediated diaphragm muscle weakness in hypertensive mice.