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Isoflurane preconditioning increases endothelial cell tolerance to in-vitro simulated ischaemia.

AbstractOBJECTIVES:
Isoflurane preconditioning has been shown to protect endothelial cells against lipopolysaccharide and cytokine induced injury. This study was designed to determine whether isoflurane preconditioning increased endothelial cell tolerance to ischaemia.
METHODS:
Bovine pulmonary arterial endothelial cells were exposed or not exposed to various concentrations of isoflurane for 1 h. After a 30-min isoflurane-free period, cells were subjected to oxygen-glucose deprivation (OGD) for 3 h and reoxygenation for 1 h. Lactate dehydrogenase release from cells was used to measure cell injury. In some experiments, various protein kinase C (PKC) inhibitors and ATP-sensitive potassium channel (K(ATP) channel) inhibitors were present from 30 min before isoflurane treatment to the end of isoflurane treatment.
KEY FINDINGS:
Isoflurane preconditioning dose-dependently decreased the OGD induced lactate dehydrogenase release. This protection was inhibited by 2 µM chelerythrine, a general PKC inhibitor, or 10 µM Gö6976, an inhibitor for the conventional PKCs. This protection was also inhibited by 0.3 µM glybenclamide, a general K(ATP) channel inhibitor, and 500 µM 5-hydroxydecanoate, a mitochondrial K(ATP) channel blocker. In addition, pretreatment with 100 µM diazoxide, a K(ATP) channel activator, for 1 h also reduced OGD induced endothelial cell injury. This diazoxide induced protection was inhibited by chelerythrine.
CONCLUSIONS:
The results suggest that isoflurane preconditioning induces endothelial protection against in-vitro simulated ischemia. This protection may be mediated at least in part by conventional PKCs and mitochondrial K(ATP) channels. The results also indicate that PKCs may be downstream of K(ATP) channels in causing endothelial protection.
AuthorsJifeng Feng, Zhiyi Zuo
JournalThe Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 63 Issue 1 Pg. 106-10 (Jan 2011) ISSN: 2042-7158 [Electronic] England
PMID21155822 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.
Chemical References
  • Anesthetics, Inhalation
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Isoflurane
  • L-Lactate Dehydrogenase
  • Protein Kinase C
Topics
  • Anesthetics, Inhalation (administration & dosage, pharmacology)
  • Animals
  • Cattle
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelial Cells (drug effects, pathology)
  • Ischemia (drug therapy, pathology)
  • Ischemic Preconditioning (methods)
  • Isoflurane (administration & dosage, pharmacology)
  • L-Lactate Dehydrogenase (metabolism)
  • Potassium Channels (metabolism)
  • Protein Kinase C (metabolism)
  • Pulmonary Artery (cytology, drug effects, pathology)

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