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Previous studies by our group have indicated that exercise intervention can ameliorate endothelial dysfunction, which is an early pathophysiological change of prediabetes mellitus. The present study aimed to test the hypothesis that nitric oxide synthases (NOSs), which are expressed in blood vessel endothelium, contribute to the mitigation of vascular endothelium-dependent dysfunction by aerobic exercise in prediabetes mellitus. A prediabetic rat model was established by feeding the rats an additional high-energy diet, and was confirmed by testing blood glucose levels, the area-under-the-curve for the blood glucose tests (P&lt;0.05) and the changes to the histological morphology of the thoracic aorta. Further examination identified that NOS expression changed significantly between the control and prediabetes groups, indicating endothelial dysfunction in the prediabetic rats. Following aerobic exercise, a significant increase in NOS, endothelial (eNOS) mRNA and protein expression (P&lt;0.05), and a significant decrease in NOS, inducible (iNOS) mRNA and protein expression (P&lt;0.05) was identified in the prediabetic rats compared with the control group. No significant change in nitric oxide synthase, brain expression was observed in the prediabetic rat group compared with the control group. Notably, there was also a significant increase and decrease in eNOS and iNOS activity, respectively, in the prediabetes group compared with the control group (P&lt;0.05). Furthermore, nitric oxide (NO) concentration in the vascular endothelium was detected, which revealed a significant increase in NO concentration in the prediabetic rats following aerobic exercise compared with the control (P&lt;0.05). The present study provided results that demonstrated that aerobic exercise ameliorated the vascular endothelium-dependent dysfunction through the NOS/NO signaling pathway, which is primarily regulated by NOS expression and activity, in prediabetes mellitus. The current study provided the theoretical basis for the use of exercise intervention to prevent diabetes mellitus during the early stage.

Effects of aerobic exercise on the expressions and activities of nitric oxide synthases in the blood vessel endothelium in prediabetes mellitus