Ketamine reduces nitric oxide biosynthesis in human umbilical vein endothelial cells by down-regulating endothelial nitric oxide synthase expression and intracellular calcium levels

Ruei-Ming Chen, Ta-Liang Chen, Yi Ling Lin, Tyng-Guey Chen, Yu-Ting Tai

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50 Citations (Scopus)

Abstract

Objective: Ketamine, an intravenous anesthetic agent, can modulate vascular tone. Nitric oxide (NO), constitutively produced in endothelial cells, contributes to vasoregulation. In this study, we attempted to evaluate the effects of ketamine on NO biosynthesis in human umbilical vein endothelial cells and its possible mechanism. Design: Controlled laboratory study Settings: Research laboratory in a universal hospital. Subjects: Human umbilical vein endothelial cells prepared from human umbilical cord veins were exposed to 1, 10, 100, and 1000 μM ketamine for 1, 6, and 24 hrs. Measurements and Main Results: Exposure to 1, 10, and 100 μM ketamine for 1, 6, and 24 hrs was not cytotoxic to human umbilical vein endothelial cells. However, kotamine at 1000 μM significantly caused cell apoptosis. A therapeutic concentration of ketamine (100 μM) time-dependently reduced the levels of nitrite in human umbilical vein endothelial cells. Immunoblot analysis revealed that ketamine time-dependently decreased endothelial NO synthase protein production in human umbilical vein endothelial cells. Results of an assay by reverse-transcription polymerase chain reaction showed that ketamine significantly inhibited levels of endothelial NO synthase messenger RNA. Ketamine time-dependently reduced bradykinin-enhanced intracellular calcium concentrations. Analysis by confocal microscopy further demonstrated the suppressive effects of ketamine on bradykinin-induced calcium mobilization. Conclusions: A clinically relevant concentration of ketamine can reduce NO biosynthesis. The suppressive mechanisms occur not only by pretranslational inhibition of eNOS expression but also by a posttranslational decrease in endothelial NO synthase activity due to a reduction in intracellular calcium levels.

Original languageEnglish
Pages (from-to)1044-1049
Number of pages6
JournalCritical Care Medicine
Volume33
Issue number5
DOIs
Publication statusPublished - May 2005

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Keywords

  • Endothelial nitric oxide synthase expression
  • Human umbilical vein endothelial cells
  • Intracellular calcium
  • Ketamine
  • Nitric oxide

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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