title: High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.
abstract: 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 H2O-2(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.
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany bows@med.uni-leipzig.de.
authors.forename: T Scott
authors.initials: TS
authors.lastname: Bowen
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Eisenkolb
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Drobner
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Werner
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Mangner
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
mesh_terms: D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000494:pharmacology; D003964:Diaphragm / Q000473:pathology*; D000072696:High-Intensity Interval Training; D006973:Hypertension; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008901:Mineralocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D008928:Mitochondria / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018908:Muscle Weakness / Q000378:metabolism / Q000517:prevention & control*; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D008901:Mineralocorticoids; D016877:Oxidants; D003900:Desoxycorticosterone
keywords: exercise; heart failure; skeletal muscle