title: Pressure-independent cerebrovascular remodelling and changes in myogenic reactivity in diabetic Goto-Kakizaki rat in response to glycaemic control.
abstract: OBJECTIVE
  We have shown hypertrophic cerebrovascular remodelling in the Goto-Kakizaki (GK) rat model of diabetes. This study tested the hypotheses that (1) vascular remodelling develops as the disease progresses and alters myogenic reactivity of resistance vessels important for regulation of cerebral blood flow (CBF), and (2) glycaemic control prevents cerebrovascular remodelling and myogenic dysfunction.
  
  
  METHODS
  Middle cerebral artery (MCA) lumen diameter, media : lumen (M : L) ratio, cross-sectional area (CSA) and myogenic tone were measured in 10- and 18-week-old control Wistar and diabetic GK rats using pressurized arteriograph (n = 8-14/group). Mean arterial blood pressure (MAP) was measured with telemetry (n = 5/group). Additional GK rats were treated with metformin (300 mg kg(-1) day(-1) ) for glycaemic control starting at 7 weeks after the onset of diabetes until 18 weeks (n = 9).
  
  
  RESULTS
  In the control group, there was no difference in remodelling indices, myogenic tone or MAP between ages. Eighteen week diabetic rats displayed increased M : L ratio and CSA, but decreased lumen diameter and myogenic tone compared to 10-week GK or 18-week control rats. MAP increased starting around 10 weeks of age and remained slightly higher in the GK rats. Glycaemic control normalized M : L ratio, CSA, lumen diameter and myogenic tone with no effect on blood pressure.
  
  
  CONCLUSIONS
  These findings suggest that diabetic rats develop MCA remodelling as the disease progresses but this is associated with impaired myogenic reactivity which may ultimately affect CBF. Our results also provide evidence that glycaemic control is an effective therapeutic strategy to prevent cerebrovascular remodelling and dysfunction.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, 30912, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kelly-Cobbs
authors.forename: M M
authors.initials: MM
authors.lastname: Elgebaly
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin