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ANESTHETIC PHARMACOLOGY

Hyperglycemia Impairs Isoflurane-Induced Adenosine Triphosphate-Sensitive Potassium Channel Activation in Vascular Smooth Muscle Cells

Takashi Kawano, MD^*, Katsuya Tanaka, MD^*, Kazuaki Mawatari, PhD, Shuzo Oshita, MD^*, Akira Takahashi, MD, and Yutaka Nakaya, MD

From the Departments of *Anesthesiology, Tokushima University School of Medicine, and Nutrition and Metabolism, Institute of Health Biosciences, Tokushima University School of Medicine, Tokushima, Japan.

Address correspondence and reprint requests to Takashi Kawano, MD, Department of Anesthesiology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Address e-mail to bass{at}clin.med.tokushima-u.ac.jp.

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) · s^–1 · 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.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999