title: Propofol depresses angiotensin II-induced cell proliferation in rat cardiac fibroblasts.
abstract: BACKGROUND
  Propofol may have beneficial effects on the prevention of angiotensin II (Ang II)-induced cardiac fibroblast proliferation via its antioxidative properties. The authors hypothesized that propofol may alter Ang II-induced cell proliferation and aimed to identify the putative underlying signaling pathways in rat cardiac fibroblasts.
  
  
  METHODS
  Cultured rat cardiac fibroblasts were pretreated with propofol then stimulated with Ang II; cell proliferation and endothelin-1 gene expression were examined. The effect of propofol on Ang II-induced nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, and activator protein 1-mediated reporter activity were also examined. The effect of propofol on nitric oxide production and protein kinase B and endothelial nitric oxide synthase phosphorylations were also tested to elucidate the intracellular mechanism of propofol in proliferation.
  
  
  RESULTS
  Ang II (100 nm) increased cell proliferation and endothelin-1 expression, which were partially inhibited by propofol (10 or 30 microm). Propofol also inhibited Ang II-increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, and activator protein 1-mediated reporter activity. Propofol was also found to increase nitric oxide generation and protein kinase B and nitric oxide synthase phosphorylations. Nitric oxide synthase inhibitor (N-nitro-L-arginine methylester) and the short interfering RNA transfection for protein kinase B or endothelial nitric oxide synthase markedly attenuated the inhibitory effect of propofol on Ang II-induced cell proliferation.
  
  
  CONCLUSIONS
  The authors' results suggest that propofol prevents cardiac fibroblast proliferation by interfering with the generation of reactive oxygen species and involves the activation of the protein kinase B-endothelial nitric oxide synthase-nitric oxide pathway.
authors.affiliation: Department of Biological Science and Technology, College of Life Sciences, China Medical University, China.
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Cheung
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Kar-Lok
authors.initials: KL
authors.lastname: Wong
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites; D015152:Blotting, Northern; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects*; D005452:Fluoresceins; D032383:Myocytes, Cardiac / Q000187:drug effects*; D019255:NADPH Oxidases / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D015742:Propofol / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014162:Transfection
chemical_list: D018686:Anesthetics, Intravenous; D000963:Antimetabolites; D018076:DNA, Complementary; D005452:Fluoresceins; D009566:Nitrates; D009573:Nitrites; C065013:2',7'-dichlorodihydrofluorescein; D013481:Superoxides; D000804:Angiotensin II; D012313:RNA; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D001973:Bromodeoxyuridine; D015742:Propofol