Sevoflurane pretreatment attenuates TNF-alpha-induced human endothelial cell dysfunction through activating eNOS/NO pathway


S. Li, J. Xu, W. Yao, H. Li, Q. Liu, F. Xiao, M. G. Irwin, Z. Xia, and W. Ruan. 2015. “Sevoflurane pretreatment attenuates TNF-alpha-induced human endothelial cell dysfunction through activating eNOS/NO pathway.” Biochem Biophys Res CommunBiochem Biophys Res CommunBiochem Biophys Res Commun, 460, Pp. 879-86.


Endothelial dysfunction induced by oxidative stress and inflammation plays a critical role in the pathogenesis of cardiovascular diseases. The anesthetic sevoflurane confers cytoprotective effects through its anti-inflammatory properties in various pathologies such as systemic inflammatory response syndrome and ischemic-reperfusion injury but mechanism is unclear. We hypothesized that sevoflurane can protect against tumor necrosis factor (TNF)-alpha-induced endothelial dysfunction through promoting the production of endothelium-dependent nitric oxide (NO). Primary cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations (0.5, 1.5 and 2.5 minimum alveolar concentration, MAC) of sevoflurane for 30 min before TNF-alpha (10 ng/mL) stimulation for 4 h. Sevoflurane pretreatment significantly reduced TNF-alpha-induced VCAM-1, ICAM-1, IkappaBalpha, and NF-kappaB activation, and blocked leukocytes adhesion to HUVECs. Meanwhile, sevoflurane (1.5 and 2.5 MAC) significantly induced endothelial nitric oxide synthase (eNOS) phosphorylation and enhanced NO levels both intracellularly and in the cell culture medium. All these cytoprotective effects of sevoflurane were abrogated by NG-nitro-l-arginine methyl ester (l-NAME), a non-specific nitric oxide synthase inhibitor. Collectively, these data indicate that sevoflurane protects against TNF-alpha -induced vascular endothelium dysfunction through activation of eNOS/NO pathway and inhibition of NF-kappaB.


1090-2104Li, SuobeiXu, JunmeiYao, WeifengLi, HaoboLiu, QingXiao, FengIrwin, Michael GXia, ZhengyuanRuan, WeiJournal ArticleResearch Support, Non-U.S. Gov'tUnited StatesBiochem Biophys Res Commun. 2015 May 8;460(3):879-86. doi: 10.1016/j.bbrc.2015.03.126. Epub 2015 Mar 31.