Propofol depresses angiotensin II-induced cell proliferation in rat cardiac fibroblasts

Tzu-Hurng Cheng, Yuk Man Leung, Chi Wai Cheung, Cheng Hsien Chen, Yen Ling Chen, Kar Lok Wong

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 μm). 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.

Original languageEnglish
Pages (from-to)108-118
Number of pages11
JournalAnesthesiology
Volume112
Issue number1
DOIs
Publication statusPublished - Jan 2010

Fingerprint

Propofol
Angiotensin II
Fibroblasts
Cell Proliferation
Proto-Oncogene Proteins c-akt
Nitric Oxide Synthase Type III
Phosphorylation
Reactive Oxygen Species
Nitric Oxide
Extracellular Signal-Regulated MAP Kinases
Transcription Factor AP-1
Endothelin-1
NADP
Nitric Oxide Synthase
Oxidoreductases
Small Interfering RNA
Transfection
Arginine
Gene Expression

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Propofol depresses angiotensin II-induced cell proliferation in rat cardiac fibroblasts. / Cheng, Tzu-Hurng; Leung, Yuk Man; Cheung, Chi Wai; Chen, Cheng Hsien; Chen, Yen Ling; Wong, Kar Lok.

In: Anesthesiology, Vol. 112, No. 1, 01.2010, p. 108-118.

Research output: Contribution to journalArticle

Cheng, Tzu-Hurng ; Leung, Yuk Man ; Cheung, Chi Wai ; Chen, Cheng Hsien ; Chen, Yen Ling ; Wong, Kar Lok. / Propofol depresses angiotensin II-induced cell proliferation in rat cardiac fibroblasts. In: Anesthesiology. 2010 ; Vol. 112, No. 1. pp. 108-118.
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