title: Hyperglycemia impairs isoflurane-induced adenosine triphosphate-sensitive potassium channel activation in vascular smooth muscle cells.
abstract: BACKGROUND
  Isoflurane activates vascular adenosine triphosphate sensitive potassium (K(ATP)) channels, and may induce vasodilation. In the present study, we investigated whether hyperglycemia modifies isoflurane activation of vascular K(ATP) channel.
  
  
  METHODS
  We used a cell-attached patch-clamp configuration to test the effects of isoflurane on K(ATP) channel activity in vascular smooth muscle cells (VSMCs) after incubation for 24 h in medium containing normal glucose (NG, 5.5 mM D-glucose), L-glucose (LG, 5.5 mM D-glucose plus 17.5 mM L-glucose), or high glucose (HG, 23 mM D-glucose). Superoxide levels in aortas were measured by the lucigenin-enhanced chemiluminescence technique.
  
  
  RESULTS
  Isoflurane-induced open probabilities were significantly reduced in VSMCs from arteries incubated in HG (0.06 +/- 0.01) compared with NG (0.17 +/- 0.02; P < 0.05) and LG (0.15 +/- 0.02; P < 0.05). Pretreatment of VSMCs with protein kinase C (PKC) inhibitors, calphostin C and PKC inhibitor 20-28, greatly reduced HG inhibition of isoflurane-induced K(ATP) channel activity. In addition, a PKC activator, PMA, mimicked the effects of HG. Superoxide release was significantly increased in arteries incubated in HG (18.3 +/- 11.5 relative light units (RLU) x s(-1) x mg(-1); P < 0.05 versus NG). Coincubated with polyethylene glycol-superoxide dismutase (250 U/mL), a cell-permeable superoxide scavenger, greatly reduced the HG-induced increase of superoxide, but failed to reduce HG inhibition of isoflurane-induced K(ATP) channel activity.
  
  
  CONCLUSIONS
  Our results suggest that the metabolic stress of hyperglycemia can impair isoflurane-induced vascular K(ATP) channel activity mediated by excessive activation of PKC. This could impede the coronary vasodilation response to isoflurane, causing ischemia or hypoxia in patients with perioperative hyperglycemia.
authors.affiliation: Department of Anesthesiology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. bass@clin.med.tokushima-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Shuzo
authors.initials: S
authors.lastname: Oshita
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D020536:Enzyme Activators / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D007530:Isoflurane / Q000494:pharmacology*; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D020536:Enzyme Activators; D016166:Free Radical Scavengers; D054086:KATP Channels; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D013481:Superoxides; D011092:Polyethylene Glycols; D007530:Isoflurane; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D011493:Protein Kinase C; C058819:calphostin C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate