title: Cerebral Cortical Microvascular Rarefaction in Metabolic Syndrome is Dependent on Insulin Resistance and Loss of Nitric Oxide Bioavailability.
abstract: OBJECTIVE
  Chronic presentation of the MS is associated with an increased likelihood for stroke and poor stroke outcomes following occlusive cerebrovascular events. However, the physiological mechanisms contributing to compromised outcomes remain unclear, and the degree of cerebral cortical MVD may represent a central determinant of stroke outcomes.
  
  
  METHODS
  This study used the OZR model of MS and clinically relevant, chronic interventions to determine the impact on cerebral cortical microvascular rarefaction via immunohistochemistry with a parallel determination of cerebrovascular function to identify putative mechanistic contributors.
  
  
  RESULTS
  OZR exhibited a progressive rarefaction (to ~80% control MVD) of the cortical microvascular networks vs. lean Zucker rats. Chronic treatment with antihypertensive agents (captopril/hydralazine) had limited effectiveness in blunting rarefaction, although treatments improving glycemic control (metformin/rosiglitazone) were superior, maintaining ~94% control MVD. Chronic treatment with the antioxidant TEMPOL severely blunted rarefaction in OZR, although this ameliorative effect was prevented by concurrent NOS inhibition.
  
  
  CONCLUSIONS
  Further analyses revealed that the maintenance of glycemic control and vascular NO bioavailability were stronger predictors of cerebral cortical MVD in OZR than was prevention of hypertension, and this may have implications for chronic treatment of CVD risk under stroke-prone conditions.
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Clinical and Translational Sciences Institute, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Chantler
authors.affiliation: Clinical and Translational Sciences Institute, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Department of Family Medicine, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Shrader
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Clinical and Translational Sciences Institute, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Division of Bariatric Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Tabone
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Division of Vascular Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: d'Audiffret
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Division of Vascular Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Khumara
authors.initials: K
authors.lastname: Huseynova
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Division of Vascular Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Brooks
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Kayla W
authors.initials: KW
authors.lastname: Branyan
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Grogg
authors.affiliation: Clinical and Translational Sciences Institute, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.|Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D020521:Stroke / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D009569:Nitric Oxide
keywords: capillary density; obesity; perfusion; rodent models of cardiovascular disease risk