Effect of compound EXP-2528 on angiotensin II-induced E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells in vitro

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 1×10^-7 mol·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.