title: Sevoflurane pretreatment attenuates TNF-α-induced human endothelial cell dysfunction through activating eNOS/NO pathway.
abstract: 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)-α-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-α (10 ng/mL) stimulation for 4 h. Sevoflurane pretreatment significantly reduced TNF-α-induced VCAM-1, ICAM-1, IκBα, and NF-κB 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-α -induced vascular endothelium dysfunction through activation of eNOS/NO pathway and inhibition of NF-κB.
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Anesthesia Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Suobei
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Anesthesia Research Institute, Central South University, Changsha, Hunan, China. Electronic address: 13975148864@139.com.
authors.forename: Junmei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong, China.
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Anesthesia Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Anesthesia Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong, China.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong, China; Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Anesthesia Research Institute, Central South University, Changsha, Hunan, China. Electronic address: ruanwei2001@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Ruan
keywords: Endothelial nitric oxide synthase; Human umbilical vein endothelial cells; Inflammation; Sevoflurane