title: Consequences of exercising on ischemia-reperfusion injury in type 2 diabetic Goto-Kakizaki rat hearts: role of the HO/NOS system.
abstract: BACKGROUND
  It is well established that physical exercise continues to be one of the most valuable forms of non-pharmacological therapy against diabetes mellitus; however, the precise mechanism remains unknown. The aim of this study was to investigate the cardioprotective effect of voluntary exercise in the Goto-Kakizaki type 2 diabetic rat heart against ischemia-reperfusion injury and to clarify its biochemical background, focusing on the nitric oxide synthase/heme oxygenase system.
  
  
  METHODS
  One group of male Goto-Kakizaki rats were allowed voluntary exercise, whereas others were kept sedentary for 6 weeks. At the end of the 6th week the hearts were isolated from both groups and subjected to 45-min coronary occlusion followed by 120-min reperfusion. The infarct size was evaluated by means of triphenyltetrazolium chloride staining. The cardiac and aortic nitric oxide synthase/heme oxygenase activities, plasma leptin and glucose concentrations were also assessed.
  
  
  RESULTS
  The sedentary state prior to the ischemia-reperfusion injury was associated with a significantly higher infarct size (24.56 ± 2.21 vs. 16.66 ± 1.87 %) as compared with that in the voluntary wheel-running group. Exercise altered the constitutive nitric oxide synthase activity; an enhancement was evident in the cardiac (42.5 ± 2.72 vs. 75.6 ± 13.34 pmol/min/mg protein) and aortic tissues (382.5 ± 66.57 vs. 576.9 ± 63.16 pmol/min/mg protein). Exercise lead to a higher heme oxygenase activity (0.68 ± 0.08 vs. 0.92 ± 0.04 nmol bilirubin/h/mg protein) in the diabetic rat hearts. Exercise was associated with lower plasma leptin (192.23 ± 7.22 vs. 169.65 ± 4.6 ng/L) and blood glucose (19.61 ± 0.76 vs. 14.58 ± 0.88 mmol/L) levels.
  
  
  CONCLUSIONS
  These results indicate the beneficial role of exercise against myocardial ischemia-reperfusion injury in diabetic rats. These observations in experimental diabetes suggest that the cytoprotective mechanism of exercise involves modulation of the nitric oxide synthase/heme oxygenase system and metabolic parameters that may be responsible for cardioprotection.
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kupai
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Renáta
authors.initials: R
authors.lastname: Szabó
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Médea
authors.initials: M
authors.lastname: Veszelka
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Amin Al
authors.initials: AA
authors.lastname: Awar
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Török
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Anett
authors.initials: A
authors.lastname: Csonka
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, University of Szeged, 6720 Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Baráth
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Pósa
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep fasor 52, 6726 Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Varga
keywords: Exercise; Heme oxygenase; Ischemia–reperfusion; Nitric oxide synthase