Differential effects of ACE and AT1 receptor inhibition on chemoattractant and adhesion molecule synthesis

Ureteral obstruction causes infiltration of the kidney by monocytes/macrophages. This infiltrate is significantly reduced by administration of an angiotensin-converting enzyme (ACE) inhibitor but not by a specific angiotensin II type I receptor (AT(1) receptor) antagonist. Chemoattractants and cell surface adhesive molecules mediate monocyte/macrophage infiltration. Rats with unilateral ureteral obstruction (UUO) of 1, 3, or 5 days duration were untreated or given enalapril or SC-51316 in the drinking water. We measured the mRNA levels of monocyte chemoatactic peptide 1 (MCP-1), a chemoattractant, and levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), two cell surface adhesion proteins. MCP-1 mRNA increased significantly after 1 day of UUO and increased further through 5 days of UUO in the obstructed kidney. ICAM-1 mRNA also increased significantly after 1 day but steadily declined through 5 days of UUO in the obstructed kidney. VCAM-1 mRNA did not increase significantly until after 3 days of UUO and increased further through 5 days of obstruction. Enalapril or SC-51316 treatment had no significant effect on ICAM-1 mRNA levels. MCP-1 mRNA levels were reduced but remained significantly elevated. Enalapril significantly blunted the increase in VCAM-1 mRNA levels and VCAM-1 protein determined by immunocytochemistry; SC-51316 had no significant effect. Thus changes in VCAM-1 levels may account for the differential effect of enalapril and SC-51316 on monocyte/macrophage infiltration of the kidney during ureteral obstruction.