Treadmill running improves hindlimb arteriolar endothelial function in type 1 diabetic mice as visualized by X-ray microangiography

BACKGROUND: Vascular function is impaired in patients with diabetes, however diabetic vascular dysfunction is ameliorated by exercise training. We aimed to clarify which hindlimb arterial segments are affected by treadmill running in the hindlimbs of streptozocin-induced type 1 diabetic mice in vivo. METHODS: Mice were divided into 3 groups; healthy control, diabetic control, and diabetic-running groups. The exercise regimen was performed by treadmill level running mice for 60 min/day, for 4 weeks. Thereafter, we examined the vascular response to systemic acetylcholine administration in the left hindlimb of anesthetized-ventilated mice using either 1) X-ray microangiography to visualize the arteries or 2) ultrasonic flowmetry to record the femoral arterial blood flow. RESULTS: X-ray imaging clearly visualized the hindlimb arterial network (~70-250 μm diameter). The vasodilator response to acetylcholine was significantly attenuated locally in the arterioles <100 μm diameter in the diabetic group of mice compared to the control group of mice. Post-acetylcholine administration, all groups showed an increase in hindlimb vascular conductance, but the diabetic mice showed the smallest increase. Overall, compared to the diabetic mice, the treadmill-running mice exhibited a significant enhancement of the vasodilator response within the arterioles with diabetes-induced vasodilator dysfunction. CONCLUSIONS: Diabetes impaired acetylcholine-induced vasodilator function locally in the arteries <100 μm diameter and decreased hindlimb vascular conductance responded to acetylcholine, while regular treadmill running significantly ameliorated the impaired vasodilator function, and enhanced the decreased conductance in the diabetic mice.