Effect of compound EXP-2528 on angiotensin II-induced E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells in vitro.
- Author:
Hui-Qing LIU
1
;
Xin-Bing WEI
;
Hai-Yan LOU
;
Bin ZHANG
;
Ru SUN
;
Xiu-Mei ZHANG
Author Information
1. School of Medicine, Shandong University, Jinan 250012, China.
- Publication Type:Journal Article
- MeSH:
Angiotensin II;
pharmacology;
Angiotensin II Type 1 Receptor Blockers;
pharmacology;
Animals;
Brain;
blood supply;
Cells, Cultured;
E-Selectin;
genetics;
metabolism;
Endothelial Cells;
metabolism;
Imidazoles;
pharmacology;
Isoxazoles;
pharmacology;
Losartan;
pharmacology;
Microvessels;
cytology;
RNA, Messenger;
metabolism;
Rats;
Vascular Cell Adhesion Molecule-1;
genetics;
metabolism
- From:
Acta Pharmaceutica Sinica
2007;42(8):822-827
- CountryChina
- Language:English
-
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.
