title: Impaired vascular KATP function attenuates exercise capacity in obese zucker rats.
abstract: OBJECTIVE
  Obese subjects exhibit decreased exercise capacity (VO2max ). We have shown that vascular KATP channel mediates arteriolar dilation to muscle contraction. We hypothesize that exercise capacity is decreased in obesity due to impaired vascular KATP function.
  
  
  METHODS
  The VO2max was measured in LZR and OZR by treadmill running before and following treatment with the KATP blocker glibenclamide i.p. One week later, the spinotrapezius muscle was prepared for in vivo microscopy. Arcade arteriolar diameters were measured following muscle contraction or application of the KATP opener cromakalim before and after glibenclamide application. In additional animals, LZR and OZR were treated with apocynin for five weeks. VO2max and arteriolar dilation experiments were repeated.
  
  
  RESULTS
  The OZR exhibited decreased VO2max , functional and cromakalim-induced vasodilation as compared with LZR. Glibenclamide had no effect on VO2max and functional vasodilation in OZR, but significantly inhibited responses in LZR. Vascular superoxide levels and NADPH oxidase activity were increased in OZR, but reduced in apocynin-treated OZR. Apocynin increased the VO2max , functional and cromakalim-induced vasodilation in OZR with no effect in LZR.
  
  
  CONCLUSIONS
  Exercise capacity is dependent on vascular KATP channel function. The reduced exercise capacity in OZR appears to be due in part to superoxide-mediated impairment in vascular KATP function.
authors: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors: Silu
authors: S
authors: Lu
authors: Lusha
authors: L
authors: Xiang
authors: John S
authors: JS
authors: Clemmer
authors: Andrew R
authors: AR
authors: Gowdey
authors: Peter N
authors: PN
authors: Mittwede
authors: Robert L
authors: RL
authors: Hester
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D019255:NADPH Oxidases / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010807:Physical Endurance; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D013481:Superoxides; C056165:acetovanillone; D019255:NADPH Oxidases; D005905:Glyburide
keywords: KATP channels; NADPH oxidase; obese; superoxide; vascular
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