title: High-intensity interval training attenuates endothelial dysfunction in a Dahl salt-sensitive rat model of heart failure with preserved ejection fraction.
abstract: Heart failure patients with preserved left ventricular ejection fraction (HFpEF) have endothelial dysfunction, but the underlying molecular mechanisms remain unknown. In addition, whether exercise training improves endothelial function in HFpEF is still controversial. The present study therefore aimed to determine the functional and molecular alterations in the endothelium associated with HFpEF, while further assessing the effects of high-intensity interval training (HIT). Female Dahl salt-sensitive rats were randomized for 28 wk into the following groups: 1) control: fed 0.3% NaCl; 2) HFpEF: fed 8% NaCl; and 3) HFpEF + HIT: animals fed 8% NaCl and HIT treadmill exercise. Echocardiography and invasive hemodynamic measurements were used to assess diastolic dysfunction. Endothelial function of the aorta was measured in vitro. Expression of endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate-oxidase [NAD(P)H oxidase], and advanced glycation end product (AGE)-modified proteins were quantified by Western blot, and zymography quantified matrix metalloproteinase (MMP) activity. In this model of HFpEF, endothelium-dependent and -independent vasodilation was impaired. However, this was prevented by HIT. In HFpEF protein expression of eNOS was reduced by 47%, but MMP-2 and MMP-9 activity was elevated by 186 and 68%. The expression of AGE-modified proteins was increased by 106%. All of these changes were prevented by HIT. Endothelial function was impaired in this model of HFpEF, which was associated with reduced expression of eNOS, increased MMP activity, and increased AGE-modified proteins. HIT was able to attenuate both these functional and molecular alterations. These findings therefore suggest HFpEF induces endothelial dysfunction, but this is reversible by HIT.
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and adav@medizin.uni-leipzig.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.affiliation: K. G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Marcia
authors.initials: M
authors.lastname: Alves
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and.
authors.forename: Tina
authors.initials: T
authors.lastname: Fischer
authors.affiliation: K. G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Natale
authors.initials: N
authors.lastname: Rolim
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Werner
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schütt
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and.
authors.forename: T Scott
authors.initials: TS
authors.lastname: Bowen
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and.
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.affiliation: University of Leipzig, Heart Center Leipzig, Leipzig, Germany; and.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.affiliation: K. G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisloff
mesh_terms: D000818:Animals; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology*; D005080:Exercise Test / Q000379:methods; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology
chemical_list: D012965:Sodium Chloride; D052250:Nitric Oxide Synthase Type III
keywords: CHF; diastolic dysfunction; eNOS; endothelial function; exercise training