title: Treadmill running improves hindlimb arteriolar endothelial function in type 1 diabetic mice as visualized by X-ray microangiography.
abstract: 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.
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan. sonobe07@gmail.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan. tsuchimo@ncvc.go.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Tsuchimochi
authors.affiliation: Department of Physiology-Heart Otago, University of Otago, Dunedin, New Zealand. daryl.schwenke@otago.ac.nz.
authors.forename: Daryl O
authors.initials: DO
authors.lastname: Schwenke
authors.affiliation: Department of Physiology, and Monash Biomedical Imaging Facility, Monash University, Melbourne, Australia. James.Pearson@monash.edu.|Australian Synchrotron, Clayton, Australia. James.Pearson@monash.edu.
authors.forename: James T
authors.initials: JT
authors.lastname: Pearson
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan. shirai@ncvc.go.jp.
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D001160:Arterioles / Q000000981:diagnostic imaging*; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging* / Q000628:therapy; D005080:Exercise Test / Q000379:methods; D006614:Hindlimb / Q000098:blood supply* / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000000981:diagnostic imaging; D010805:Physical Conditioning, Animal / Q000379:methods*; D012420:Running