Consequences of exercising on ischemia–reperfusion injury in type 2 diabetic Goto-Kakizaki rat hearts: role of the HO/NOS system

Abstract

BackgroundIt 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.MethodsOne 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.ResultsThe 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-015-0080-x) contains supplementary material, which is available to authorized users.

Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits

“…The heat shock protein HO-1 (hsp-32) is a major antioxidant defense enzyme, which is increased in response to trauma intrinsic to a wide range of diseases, including (and especially) atherosclerotic syndromes [ 35 ]. Often, the effects of a disease process overwhelm the protective capacity afforded by endogenous HO-1 expression [ 36 , 37 , 38 ]. However, its cardioprotective effects may be greatly amplified by the administration of pharmacological inducers, as demonstrated by the authors of the present report [ 28 ].…”

Experimental Diabetes Mellitus in Different Animal Models

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Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection

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