title: Temporal development of retinal arteriolar endothelial dysfunction in porcine type 1 diabetes.
abstract: OBJECTIVE
  Although hyperglycemia is implicated in retinal vascular dysfunction associated with the development of diabetic retinopathy, the temporal influence of hyperglycemia on retinal arteriolar reactivity remains unclear. Development of a large animal model of diabetes relevant to the human retina for evaluation of vascular function is also lacking. Herein, we examined nitric oxide (NO)-mediated dilation and endothelin-1 (ET-1)-induced constriction in retinal arterioles at various time periods in a porcine model of type 1 diabetes.
  
  
  METHODS
  Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2, 6, and 12 weeks of hyperglycemia, 427 ± 23 mg/dL) and age-matched control pigs (73 ± 4 mg/dL), and then cannulated and pressurized for vasoreactivity study using videomicroscopic techniques.
  
  
  RESULTS
  Retinal arterioles isolated from control and diabetic pigs developed comparable levels of myogenic tone. The endothelium-dependent NO-mediated vasodilations to bradykinin and stepwise increases in luminal flow were significantly reduced within 2 weeks of hyperglycemia. The inhibitory effect was comparable following 6 and 12 weeks of hyperglycemia. However, the endothelium-independent vasodilation to sodium nitroprusside was unaffected. Constriction of retinal arterioles to ET-1 was unaltered at all time periods of hyperglycemia.
  
  
  CONCLUSIONS
  Our findings provide the first direct evidence for selective impairment of endothelium-dependent NO-mediated dilation of retinal arterioles within 2 weeks of hyperglycemia in a pig model of diabetes. By contrast, the ability of arteriolar smooth muscle to dilate to NO donor or contract to ET-1 was unaffected throughout the study period. This endothelial vasodilator dysfunction during early diabetes may contribute to development of retinopathy with chronic hyperglycemia.
authors.affiliation: Department of Surgery, Scott & White Memorial Hospital, College of Medicine, Texas A&M Health Science Center, Temple, Texas 76504, USA. thein@tamu.edu
authors.forename: Travis W
authors.initials: TW
authors.lastname: Hein
authors.forename: Luke B
authors.initials: LB
authors.lastname: Potts
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xu
authors.forename: Josh Z
authors.initials: JZ
authors.lastname: Yuen
authors.forename: Lih
authors.initials: L
authors.lastname: Kuo
mesh_terms: D000818:Animals; D001160:Arterioles / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D012161:Retinal Artery / Q000473:pathology*; D034421:Sus scrofa; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D014665:Vasodilator Agents; D009569:Nitric Oxide