title: Effects of propofol on cyclic strain-induced endothelin-1 expression in human umbilical vein endothelial cells.
abstract: BACKGROUND
  Propofol is one of the most popular intravenous induction agents of general anesthesia. Experimental results revealed that propofol exerted hypotensive and antioxidative effects. However, the intracellular mechanism of propofol remains to be delineated. The aims of this study were to test the hypothesis that propofol may alter strain-induced endothelin-1 (ET-1) secretion and nitric oxide production, and to identify the putative underlying signaling pathways in human umbilical vein endothelial cells.
  
  
  METHODS
  Cultured human umbilical vein endothelial cells were exposed to cyclic strain in the presence of propofol, and ET-1 expression was examined by Northern blotting and enzyme-linked immunosorbent assay kit. Activation of extracellular signal-regulated protein kinase, endothelial nitric oxide synthase, and protein kinase B were assessed by Western blot analysis.
  
  
  RESULTS
  The authors show that propofol inhibits strain-induced ET-1 expression, strain-increased reactive oxygen species formation, and extracellular signal-regulated protein kinase phosphorylation. On the contrary, nitric oxide production, endothelial nitric oxide synthase activity, and protein kinase B phosphorylation were enhanced by propofol treatment. Furthermore, in the presence of PTIO, a nitric oxide scavenger, and KT5823, a specific inhibitor of cyclic guanosine monophosphate-dependent protein kinase, the inhibitory effect of propofol on strain-induced extracellular signal-regulated protein kinase phosphorylation and ET-1 release was reversed.
  
  
  CONCLUSIONS
  The authors demonstrate for the first time that propofol inhibits strain-induced ET-1 secretion and enhances strain-increased nitric oxide production in human umbilical vein endothelial cells. Thus, this study delivers important new insight into the molecular pathways that may contribute to the proposed hypotensive effects of propofol in the cardiovascular system.
authors.affiliation: Department of Biological Science and Technology, School of Life Science, China Medical University, Taichung, Taiwan.
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.forename: Jin-Jer
authors.initials: JJ
authors.lastname: Chen
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Kar-Lok
authors.initials: KL
authors.lastname: Wong
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015742:Propofol / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D019332:Endothelin-1; D017382:Reactive Oxygen Species; D015742:Propofol