Effect of compound EXP-2528 on angiotensin II-induced E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells in vitro / 药学学报
Acta Pharmaceutica Sinica
; (12): 822-827, 2007.
Article
in En
| WPRIM
| ID: wpr-268572
Responsible library:
WPRO
ABSTRACT
The aim of this study is to investigate the effect and mechanism of angiotensin (Ang) II on E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression in rat brain microvascular endothelial cells (BMEC) and evaluate the effect of compound EXP-2528, a novel Ang II type 1 (AT1) receptor antagonist. The experiment was performed in cultured BMEC of rat. The mRNA and protein expression of E-selectin and VCAM-1 in BMEC was analyzed by RT-PCR and Western blotting, respectively. The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMEC were significantly upregulated by 4 h or 18 h exposure to 1 x 10(-7) mol x L(-1) Ang II. These effects were abolished by pretreatment with the selective AT1 receptor antagonists losartan and compound EXP-2528, but not with the AT2 selective antagonist PD123319. Combining losartan with PD123319 also significantly inhibited Ang II-induced E-selectin and VCAM-1 expression in BMEC, but there was no significant difference compared with losartan group. These findings indicated that Ang II upregulated E-selectin and VCAM-1 in BMEC by activating AT1 receptor and then involved in the development of cerebrovascular disease.
Full text:
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Index:
WPRIM
Main subject:
Pharmacology
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Brain
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RNA, Messenger
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Angiotensin II
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Cells, Cultured
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Vascular Cell Adhesion Molecule-1
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E-Selectin
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Losartan
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Cell Biology
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Endothelial Cells
Limits:
Animals
Language:
En
Journal:
Acta Pharmaceutica Sinica
Year:
2007
Type:
Article