title: Differential impact of dilator stimuli on increased myogenic activation of cerebral and skeletal muscle resistance arterioles in obese zucker rats.
abstract: OBJECTIVE
  To use the OZR model of the metabolic syndrome to determine the impact of dilator stimuli on MA of GA and MCA. We tested the hypothesis that increased oxidant stress and TxA2 exacerbate MA, and prevent its blunting with dilator stimuli, in OZR.
  
  
  METHODS
  GA/MCA from OZR and LZR was pressurized ex vivo. MA was determined under control conditions and following challenge with acetylcholine, hypoxia, and adenosine. Responses were also evaluated after pre-treatment with TEMPOL (antioxidant) and SQ-29548 (PGH2 /TxA2 receptor antagonist).
  
  
  RESULTS
  MA was increased (and dilator responses decreased) in GA/MCA from OZR, dependent on the endothelium and ROS. In GA, the impact of ROS on MA and dilator effects was largely via TxA2 , while in MCA, this appeared was more dependent on NO bioavailability. Intrinsic responses of GA/MCA to carbacyclin, U46619, and NO donors were similar between strains.
  
  
  CONCLUSIONS
  A developing ROS-based endothelial dysfunction in MCA and GA of OZR contributes to an enhanced MA of these vessels. Although treatment of GA/MCA with TEMPOL attenuates MA in OZR, the mechanistic contributors to altered MA, distal to ROS, differ between the two resistance vessels.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia, USA; Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Butcher
authors.forename: Adam G
authors.initials: AG
authors.lastname: Goodwill
authors.forename: Shyla C
authors.initials: SC
authors.lastname: Stanley
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D017382:Reactive Oxygen Species / Q000378:metabolism; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D017382:Reactive Oxygen Species
keywords: microcirculation; peripheral resistance; regulation of vascular tone; rodent models of metabolic syndrome