Roles of vitamin C and exercise training on endothelial dysfunction in diabetic rats

Abstract

Determines the protective effects of vitamin C supplementation and exercise training on the diabetic endothelial dysfunction (ED). Male Spraque-Dawley rats were divided into five groups of control (Con), diabetes (DM), diabetes with supplemented vitamin C (DM+Vit.C), diabetes with exercise- trained (DM+Ex) and diabetes with supplemented vitamin C and exercise- trained (DM+Vit.C+Ex) groups. Diabetes was induced by intravenous injection of streptozotocin (STZ;50 mg/kgBW). Vitamin C was given in drinking water with the concentration of 1 g/L. The exercise training protocol consisted of treadmill running 5 times/week with velocity 13-15 m/min for 30 min. The results showed that either 12 and 24 weeks (wk) after the STZ injection, blood glucose (BG), glycosylated hemoglobin (HbA1C), arterial blood pressure (BP), heart weight (HW) and plasma triglyceride (Trig) were significantly higher and lower in plasma vitamin C levels in DM rats. In DM+Vit.C rats,the plasma vitamin C levels and HbA1C were significantly increased (P<0.05). However, BP were decreased in DM+Vit.C rats. Whereas DM+Ex rats had reduced the abnormalities of BP and HW when compared with DM rats and had a significant decrease in heart rate compared to Con rats. To examine the effects of vitamin C supplementation and exercise training on ED, leukocyte-endothelial cell (EC) interaction in mesenteric venules and vascular reactivity response to vasodilators in mesenteric arterioles were monitored using intravital fluorescence microscopy. It was found that the diabetic state enhanced leukocyte adhesion and impaired vasodilatory response to the EC-dependent vasodilator, Ach, either 12- and 24- wk. The increase of leukocyte adherance was attenuated by supplemented with vitamin C and exercise training. The impaired vascular reactivity to Ach was found to be attenuated by supplemented vitamin C. However, it failed to improve the impairment of EC-dependent vasodilation by exercise training. In addition, vitamin C and training were also shown to have favorable effects on oxidative stress and antioxidant status. DM rats had significantly higher in malondialdehyde (MDA) level and lower activity of superoxide dismutase (SOD) than Con rats. However, the MDA levels in DM+Vit.C and DM+Ex were significantly lower than those of DM rats and there were no significant differences in SOD activity among DM+Vit.C and DM+Ex compared to Con group. Moreover, the decreased eNOS protein in DM rats was prevented by vitamin C supplemented. Interestingly, we found the combined protective roles of supplemented with vitamin C and exercise training in DM+Vit.C+Ex group as well. They showed the more beneficial influence both in cardiovascular fitness and endothelial function in diabetic rats. In conclusion, our observations indicated that the endothelial dysfunction of diabetic rats is associated with increased leukocyte adhesion and impaired endothelium-dependent relaxation. However, vitamin C supplementation combined with exercise training could prevent these deleterious effects by ameliorating the diabetic-induced imbalance of oxidants/antioxidants. Therefore, vitamin C supplementation and regular exercise training might be an effective and inexpensive therapeutic modality in preventing diabetic cardiovascular complications which were crucially induced through the endothelial dysfunction in diabetes.