Bay w 9798, a dihydropyridine structurally related to nifedipine with no calcium channel-blocking properties, inhibits tumour necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in endothelial cells by suppressing reactive oxygen species generation.

Abstract

Dihydropyridine-based calcium antagonists (DHPs) are widely used to treat hypertension. We have previously shown that nifedipine, one of the most popular DHPs, blocks tumour necrosis factor-alpha (TNF-alpha)-induced monocyte chemoattractant protein-1 as well as vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells by suppressing reactive oxygen species generation (ROS). The molecular mechanism is still to be elucidated, however, because endothelial cells do not possess voltage-operated L-type calcium channels. The aim of this study was to determine in TNF-alpha-exposed human umbilical vein endothelial cells (HUVECs) whether and how Bay w 9798, a dihydropyridine structurally related to nifedipine with no calcium antagonistic properties, may suppress VCAM-1 expression, a key molecule which mediates the adhesion of monocytes to vasculature in the early stages of atherosclerosis. In HUVECs, 10 ng/ml TNF-alpha for 4 h stimulated ROS generation and subsequently upregulated VCAM-1 mRNA levels, both of which were dose-dependently blocked by Bay w 9798. The results demonstrated that Bay w 9798 inhibited VCAM-1 expression in TNF-alpha-exposed cells by suppressing ROS generation. They suggest that the anti-inflammatory and anti-oxidative properties of nifedipine and Bay w 9798 may be ascribed to the dihydropyridine structure, which is common to both molecules and has no calcium antagonistic ability.

• Authors: T Matsui, S Yamagishi, K Nakamura, H Inoue
• Journal: The Journal of international medical research (J Int Med Res) 2007 Nov-Dec Vol. 35 Issue 6 Pg. 886-91 ISSN: 0300-0605 [Print] England
• PMID: 18084847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bay w 9798
• Calcium Channel Blockers
• Dihydropyridines
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Nifedipine

Topics

• Calcium Channel Blockers (chemistry, metabolism)
• Cell Line
• Dihydropyridines (chemistry, metabolism, pharmacology)
• Dose-Response Relationship, Drug
• Endothelial Cells (cytology, drug effects, metabolism)
• Humans
• Molecular Structure
• Nifedipine (chemistry, metabolism)
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)