Protective Effect of Exercise Training plus Vitamin C supplementation on Endothelial Dysfunction in Diabetic Rats

Abstract

PURPOSE: To determine the protective effects of exercise training plus vitamin c supplementation on diabetic endothelial dysfunction (ED). METHODS: Male Spraque-Dawley rats (n=28) were divided into four groups; control (Con), diabetes (DM), diabetes with exercise training (DM+Ex) and diabetes with exercise training plus supplemented vitamin c (DM+Ex+Vit.c). Diabetes was induced by intravenous injection of streptozotocin (STZ;50 mg/kgBW). The exercise training protocol consisted of treadmill running 5 times/week with velocity 13–15 m/min for 30 min. Vitamin c was given in drinking water with the concentration of 1 g/L. To examine ED, leukocyte adhering in mesenteric venules and vascular reactivity response to the endothelial cell-dependent vasodilator, Ach in mesenteric arterioles were monitored using intravital fluorescence microscopy. Muscle malondialdehyde level (MDA) and activity of superoxide dismutase (SOD) as well as endothelial nitric oxide synthase protein level (eNOS) in heart was also measured. RESULTS: At 24- wk, the diabetic state enhanced leukocyte adhesion (5.57+0.97 vs 11.86+0.86 cells/100 um) and impaired vasorelaxation (12.59+1.45 vs 3.24+0.51 %). The increase of leukocyte adherence was attenuated in both DM+Ex (5.13+0.70 cells/100 um, P < 0.001) and DM+Ex+Vit.c (5.14 +0.67 cells/100 um, P < 0.001). However, the impaired vasorelaxation was found to be increased in only DM+Ex+Vit. c (9.62+1.66 %, P < 0.05). MDA of DM+Ex (2437.43+251.55 nmole/g wet wt.) and DM+Ex+Vit.c (1947.38+143.57 nmole/g wet wt.) were significantly lower (P < 0.01) than those of DM (2843.83+286.42 nmole/g wet wt.). DM had significantly lower in SOD (P < 0.05) than Con but there were no significant differences in SOD activity among DM+Ex, DM+Ex+Vit.c and Con. It failed to improve the decreased eNOS in DM+Ex (1.57 +0.81 ug /5μg Protein) but not in DM+Ex+Vit.c (4.35 +0.40 ug /5μg Protein, P < 0.05) when compared with DM (1.45 +0.66 ug /5μg Protein). CONCLUSION: Regular exercise training combined with vitamin c supplementation is an effective therapeutic modality to prevent diabetic endothelial dysfunction by ameliorating the diabetic-induced imbalance of oxidants/antioxidants.