Details

Autor(en) / Beteiligte

• Feng, Jifeng
• Zuo, Zhiyi

Titel

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

Ist Teil von

• Journal of pharmacy and pharmacology, 2011-01, Vol.63 (1), p.106-110

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Objectives  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 (KATP 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 KATP channel inhibitor, and 500 µM 5‐hydroxydecanoate, a mitochondrial KATP channel blocker. In addition, pretreatment with 100 µM diazoxide, a KATP 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 KATP channels. The results also indicate that PKCs may be downstream of KATP channels in causing endothelial protection.