The upregulation of ICAM-1 and P-selectin requires high blood pressure but not circulating renin–angiotensin system in vivo

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Abstract

Objective

To investigate the separate contributions of blood pressure and the circulating renin–angiotensin system to the upregulation of vascular endothelial adhesion molecules in vivo.

Methods

One or 4 weeks after constriction of the abdominal aortas of Wistar rats, the expressions of intercellular adhesion molecule-1 (ICAM-1), P-selectin, nuclear factor (NF) κB p65 subunit and monocytes were assessed at sites proximal and distal to the site of constriction, by western blot, immunohistochemistry, or both.

Results

At 1 week, the mean arterial pressure was increased significantly at the cervical artery in the group with aortic constriction (160 ± 4 mmHg, compared with 104 ± 2 mmHg before constriction), but not at the femoral artery (111 ± 10 mmHg, compared with 100 ± 2 mmHg before constriction) (P< 0.05), and circulating angiotensin II was increased significantly only in the group with aortic constriction (124 ± 28 pg/ml, compared with 14 ± 2 pg/ml in the sham-operated group; P< 0.05). In the aorta-constricted group, the expressions of ICAM-1, P-selectin, and NF-κB p65 subunit were significantly upregulated (2–3.1-fold) at the aorta proximal to the constriction compared with those distal to it, which were the same as those in the sham-operated group. Immunolocalization of these molecules was observed to be on the endothelial cells. Adhesive monocytes on the endothelium were also increased significantly only proximal to the constriction in the aorta-constricted group. At 4 weeks the findings were the same, except that circulating angiotensin II was within the normal range in both the aorta-constricted and the sham-operated groups.

Conclusions

Our results indicate that the high blood pressure, but not the circulating renin–angiotensin system, upregulates the expression of ICAM-1and P-selectin, suggesting that mechanical forces may be more important than humoral factors in the upregulation of adhesion molecules in hypertension.

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