Extracellular Signal-Regulated Kinases Trigger Isoflurane Preconditioning Concomitant with Upregulation of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Expression in Rats
| Autor: | Martin Bienengraeber, David C. Warltier, Chen Wang, Dorothee Weihrauch, Judy R. Kersten, David A. Schwabe, Phillip F. Pratt, Paul S. Pagel |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Minimum alveolar concentration medicine.medical_treatment chemistry.chemical_compound Internal medicine medicine Animals Phosphorylation Rats Wistar Extracellular Signal-Regulated MAP Kinases Cardioprotection Isoflurane business.industry Growth factor Hypoxia-Inducible Factor 1 alpha Subunit Rats Up-Regulation Vascular endothelial growth factor Anesthesiology and Pain Medicine Endocrinology Gene Expression Regulation chemistry Coronary occlusion Anesthetics Inhalation Ischemic Preconditioning Myocardial Anesthetic Ischemic preconditioning business medicine.drug |
| Zdroj: | Anesthesia & Analgesia. 103:281-288 |
| ISSN: | 0003-2999 |
| DOI: | 10.1213/01.ane.0000226094.94877.98 |
| Popis: | INTRODUCTION Extracellular signal-related kinases 1 and 2 (Erk1/2) are mitogen-activated protein kinases that have been implicated in anesthetic preconditioning; but whether Erk1/2 triggers or mediates this beneficial effect and the mechanisms by which Erk1/2 produces cardioprotection are unknown. We tested the hypothesis that isoflurane preconditioning is triggered by Erk1/2 concomitant with upregulation of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression in rats instrumented for hemodynamic measurement and subjected to a 30-min coronary artery occlusion and 2-h reperfusion. METHODS Rats randomly received IV 0.9% saline (control) or isoflurane (1.0 minimum alveolar concentration administered for 30 min and discontinued 15 min [memory period] before coronary occlusion) in the absence or presence of the selective Erk1/2 inhibitor PD 098059 (1 mg/kg in dimethylsulfoxide administered IV either 3 min before exposure to isoflurane [trigger] or 3 min after discontinuation of the drug [mediator]). Additional rabbits were pretreated with dimethylsulfoxide alone. Left ventricular tissue samples were obtained at selected intervals from additional groups of rats for Western immunoblot analysis of phospho-Erk1/2, HIF-1alpha, and VEGF protein expression. RESULTS Isoflurane significantly (P < 0.05) reduced infarct size (41% +/- 8% of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (59% +/- 4%). PD 098059 administered before, but not after, isoflurane abolished this cardioprotection (61% +/- 5% and 42% +/- 9%, respectively). Isoflurane-induced increases in phospho-Erk1/2, HIF-1alpha, and VEGF expression were also inhibited by PD 098059 pretreatment. CONCLUSIONS The results indicate that Erk1/2 triggers isoflurane preconditioning concomitant with HIF-1alpha and VEGF upregulation in vivo. |
| Databáze: | OpenAIRE |
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