title: Differential effects of ACE and AT1 receptor inhibition on chemoattractant and adhesion molecule synthesis.
abstract: 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 1 receptor (AT1 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA. morrisse@imgate.wustl.edu
authors.forename: J J
authors.initials: JJ
authors.lastname: Morrissey
authors.forename: S
authors.initials: S
authors.lastname: Klahr
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014230:Triazoles; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C075064:SC 51316; D004656:Enalapril