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Title 

Midazolam inhibits tumor necrosis factor-alpha-induced endothelial activation: involvement of the peripheral benzodiazepine receptor

Authors 

H K JooS C OhE J ChoKyoungsook ParkJ Y LeeE J LeeS K LeeH S KimJ B ParkB H Jeon

Publisher 

Lippincott, Williams & Wilkins

Issue Date 

2009

Citation 

Anesthesiology, vol. 110, no. 1, pp. 106-112

Keywords 

4 aminobutyric acid receptormidazolamtumor necrosis factor alphaendothelial cellsreceptors, GABA

Abstract 

BACKGROUND: Midazolam is widely used as an intravenous sedative. However, the role of midazolam on vascular endothelial activation is still unknown. The present study explores the action of midazolam on endothelial activation and its role to peripheral benzodiazepine receptor (PBR) in cultured human umbilical vein endothelial cells. METHODS: Intracellular localization of PBR in human umbilical vein endothelial cells was visualized with immunofluorescent staining. Monocyte adhesion and vascular cell adhesion molecule-1 expression were measured with monocyte adhesion assay and Western blot analysis. Involvement of PBR was assessed by using specific antagonists and small interfering RNA against PBR. RESULTS: PBR was localized in the mitochondria of human umbilical vein endothelial cells. Midazolam significantly inhibited tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 and monocyte adhesion in a dose-dependent manner (1-30 microM). The midazolam-mediated suppression on the tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression and monocyte adhesion were inhibited by the pretreatment of PK11195 and not inhibited by the flumazenil. Transfection of small interfering RNA for PBR decreased the expression of PBR (18 kDa) in human umbilical vein endothelial cells. Midazolam-mediated suppression on the tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression was abrogated by the transfection of small interfering RNA for PBR. CONCLUSION: These results suggest that midazolam has an inhibitory action on the endothelial activation and that its action is related to the activation of peripheral benzodiazepine receptor localized in mitochondria of the endothelial cells.

ISSN 

0003-3022

Link 

http://dx.doi.org/10.1097/ALN.0b013e318190bc69

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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